bluuebunny/crossref_metadata_2025 huggingface dataset:
Interleukin-1β (IL-1β), IL-1 receptor antagonist, and TNFα production in whole blood
Authors: Nerad Judith L , Griffiths Jeffrey K , Jos WM , Van der Meer  , Endres Stefan , Poutsiaka Debra D , Keusch Gerald T , Bennish Michael , Salam Mohammed A , Dinarello Charles A , Cannon Joseph G
Published: January 2018

The ability of an individual to mount defense responses to infection depend in part on the capacity to produce cytokines such as interleukin 1 (IL-1) and tumor necrosis factor (TNF). The specialized equipment, labor intensity, and sterile practice required for the standard in vitro evaluation of cytokine production can make such evaluation impractical in some clinical situations. We report a method for stimulating whole blood to produce cytokines that can be implemented in laboratories without tissue culture facilities and requires minimal sample preparation. IL-1β and TNFβ production in whole blood samples was stimulated with endotoxin and/or phyto- hemagglutinin in standard EDTA-containing vacuum collection tubes. After incubation, plasma was removed and frozen for later assay. Comparison of this whole blood method with isolated mononuclear cell cultures indicated a significant correlation for IL-1β production (r = 0.746, β = 0.005). This technique also produced the newly described cytokine, IL-1 receptor antagonist. We conclude that the whole blood method is an acceptable alternative to isolated cell culture methods for measuring IL-1β in situations that preclude the standard in vitro approach.
Expression and complex assembly of calcium-binding proteins MRP8 and MRP14 during differentiation of murine myelomonocytic cells
Authors: Goebeler Matthias , Roth Johannes , Henseleit Ute , Sunderkotter Cord , Sorg Clemens
Published: January 2018

In the present study we analyzed expression and biochemical properties of the two recently cloned calcium-binding proteins MRP8 and MRP14, both members of the S-100 family, in murine myelomonocytic cells. Expression of MRPs was found to be restricted to granulocytes and distinct stages of macrophage differentiation when compared to the expression of other markers (Mac-1, F4/80) in transformed macrophage cell lines (Ml, RMB.TG, WEHI.TG, J774A, P388D) and resident and exudate peritoneal and tissue macrophages. Similarly, mRNA and protein levels of MRP8/MRP14 in murine bone marrow cells decreased during culture in L cell-conditioned medium. Applying a cross-linking technique, the formation of noncovalently associated heteromeric MRP8/MRP14 complexes of 25, 35, and 48 kd was demonstrated. Our data suggest that MRP8/MRP14 expression and complexation are characteristic for granulocytes and distinct stages of macrophage differentiation in mice. Analysis of the MRP8/MRP14+ phenotype of macrophages may provide further insights into the mechanisms underlying macrophage differentiation. J. Leukoc. Biol. 53: 11–18; 1993.
Characterization of interleukin-1 and interleukin-6 production by hepatic endothelial cells and macrophages
Authors: Feder Lisa S , Todaro Jeanine A , Laskin Debra L
Published: January 2018

Interleukin-1 (EL-1) and interleukin-6 (IL-6) derived from Kupffer cells are major inducers of hepatic inflammation and the acute phase response. The present studies demonstrate that liver endothelial cells also produce significant quantities of IL-1 and IL-6, suggesting that these cells also participate in these processes. Endothelial cells and macrophages were isolated from female Sprague-Dawley rats by combined collagenase and pronase perfusion of the liver followed by centrifugal elutriation. In the absence of stimulation, endothelial cells were found to spontaneously produce IL-1 and IL-6 in a time-dependent manner, reaching maximal levels after 10 h in culture for IL-1 and 6-8 h for EL-6. The amount and kinetics of cytokine production by hepatic endothelial cells were similar to those observed with Kupffer cells. In further studies, the effects of lipo- polysaccharide (LPS), a potent liver macrophage activator and inflammatory agent, on cytokine release were analyzed. Treatment of rats with LPS resulted in a decrease in IL-1 release by both cell types compared to cells from untreated animals. In contrast, LPS treatment had no major effect on IL-6 release. We also found that both macrophages and endothelial cells could be induced to produce additional IL-1 and IL-6 by treatment with LPS in vitro, but only if they were preincubated for at least 24 h prior to stimulation with LPS and analyzed for cytokine release. These data demonstrate that liver endothelial cells, like Kupffer cells, have the capacity to produce immunoregulatory and proinfiammatory cytokines. J. Leukoc. Biol. 53: 126–132; 1993.
Cytokine mRNA expression in livers of mice infected with Listeria monocytogenes
Authors: Wagner R Doug , Czuprynski CJ
Published: January 2018

Temporally distinct groups of cytokine expression were observed by reverse transcription-polymerase chain reaction assay, in situ hybridization, and immuno- histochemistry in the livers of Listeria monocytogenes- infected mice. One group consisted of interferon-7 (IFN- γ), tumor necrosis factor a (TNF-α), and interleukin-10 (IL-10), for which mRNAs were induced within 1 day after challenge. A second group consisted of IL-2 and IL-4, for which mRNA was strongly expressed at 1 day but then suppressed at 3 days into the infection. Granulocyte- macrophage colony-stimulating factor (GM-CSF), IL-la, and IL-6 mRNA constituted a third group, which was increased at 3 days after challenge. Distributions of cytokine mRNA-expressing cells in the liver was observed by in situ hybridization. Cells expressing TNF-α and IL-lα mRNA were present throughout liver granulomas, whereas cells that expressed IFN-γ mRNA were observed mostly along the periphery of granulomas. Cells expressing IL-2, IL-4, IL-6, IL-10, and GM-CSF mRNA were distributed principally in the hepatic sinuses. Cells expressing IL-10 mRNA increased in number early in the infection when L. monocytogenes was multiplying in the liver. We conclude that cytokine mRNA expression during the early phases of L. monocytogenes infection in mice is temporally regulated and that IFN-7, TNF-α, and IL-lα are expressed by cells associated with hepatic granulomas. J. Leukoc. Biol. 53: 525–531; 1993.
Up-regulation of neutral endopeptidase (CALLA) in human neutrophils by granulocyte-macrophage colony-stimulating factor
Authors: Connelly Jon C , Chambless Robin , Holiday David , Chittenden Kim , Johnson Alice R
Published: January 2018

Neutral endopeptidase 24.11 (NEP/CALLA/ CD10), an enzyme expressed on early lymphoid progenitors, neutrophils, and various other cell types, inactivates many biologically active peptides, including the bacterial chemo- tactic peptide M-formylmethionyl-leucyl-phenylalanine (fMLP). Inhibition of CD10/NEP on the surface of human neutrophils (PMNs) in vitro inhibits migration toward this chemotaxin, suggesting that enzymatic inactivation by NEP regulates the neutrophil response to fMLP. Because PMNs in inflammatory sites are exposed to various cytokines, we evaluated the effects of selected cytokines on CD10/NEP activity in vitro. Of five cytokines tested—interleukin-1 (IL-1), IL-6, and IL-8, granulocyte colony-stimulating factor, and granulocyte- macrophage colony-stimulating factor (GM-CSF) —GM- CSF provided the most consistent increase in surface NEP activity. Low concentrations (10−9-10−7 M) of GM- CSF increased NEP activity in a time- and concentration- dependent manner to more than 225% that of control (phosphate-buffered saline-treated) cells. Cytofluorome- try of cells stained with a fluorescent antibody to CD10 indicated that GM-CSF increased expression of surface CD10/NEP antigen in a similar manner. The effect of GM-CSF on NEP activity was enhanced still further by simultaneous exposure to IL-1, suggesting that combinations of cytokines may direct and regulate the neutrophil response within an inflammatory site. Rapid up- regulation of CD10/NEP underscores the importance of this enzyme for control of peptide mediators of inflammation. J. Leukoc. Biol. 53: 685–690; 1993.
TGF-beta1 inhibits both endotoxin-induced prostaglandin synthesis and expression of the TIS10/prostaglandin synthase 2 gene in murine macrophages
Authors: Reddy Srinivasa T , Gilbert Rebecca S , Xie Weilin , Luner Steven , Herschman Harvey R
Published: January 2018

Activated macrophages produce substantial quantities of paracrine mediators, including cytokines, nitric oxide, and prostaglandins. Transforming growth factor beta1 (TGF-beta) is a potent modulator of immune function. TGF-beta inhibits the cytotoxic activity of en-dotoxin/lipopolysaccharide (LPS)-activated macrophage cell lines and primary macrophage cultures, reducing their expression of cytokines and nitric oxide. In this report we demonstrate that TGF-beta also attenuates the LPS-induced synthesis and secretion of prostaglandin E2 in murine RAW 264.7 macrophage cells. Macrophage activation also induces accumulation of the recently described ligand-responsive prostaglandin synthase (PGS) TIS10/PGS-2. While TGF-beta alone has no effect on expression from the TIS10/PGS-2 gene, this cytokine inhibits LPS-induced TIS10/PGS-2 protein accumulation and synthesis, as well as LPS-induced TIS10/PGS-2 message accumulation in RAW 264.7 cells. TGF-beta concentrations in the range of 0.1–1.0 ng/ml (4–40 pM) maximally inhibit LPS-induced TIS10/PGS-2 message accumulation. In contrast, neither LPS nor TGF-beta has any effect on the level of PGS-1 (EG 1.14.99.1) message. TGF-beta also attenuates LPS-induced accumulation of unspliced TIS10/PGS-2 transcripts in RAW 264.7 cells, suggesting that this cytokine exerts its effects on TIS10/PGS-2 expression at the transcriptional level. TGF-beta inhibits the LPS-induced accumulation of TIS10/PGS-2 protein and message in cultured murine peritoneal macrophages, as well as in macrophage cell lines. J. Leukoc. Biol. 55: 192–200; 1994.
Involvement of CD4 in interleukin-6 secretion by U937 monocytic cells stimulated with the lectin jacalin
Authors: Taimi Mohammed , Dornand Jacques , Nicolas Michel , Marti Jacques , Favero Jean
Published: January 2018

The lectin jacalin is mitogenic for CD4 expressing T lymphocytes, interacts with the CD4 molecule, and inhibits HIV infection of CD4+ cells. In the present study the effect of jacalin was tested on cells from the monocyte/macrophage lineage that also express the CD4 molecule. We used CD4+ promyelomonocytic U937 cells differentiated towards the monocytic/macrophage lineage with either a mixture of two physiological agents, retinoic acid (RA) and 1α,25-dihydroxyvitamin D3 (VD), or the exogenous drug phorbol myristate acetate (PMA). The cells resulting from these treatments differed in term of CD4 expression. We focused our attention on interleukin-6 (IL-6) production, which implies an activation of the cells differentiated along both pathways. In CD4+ RA/VD-treated cells, jacalin induced a 10-fold higher IL-6 secretion than did lipopolysaccharide (LPS). This jacalin-induced IL-6 production was inhibited by agents interacting with CD4 (anti-CD4 mAbs and HIV recombinant gp120) or by recombinant soluble CD4. In contrast, the CD4- PMA-differentiated U937 cells did not secrete any IL-6 upon jacalin treatment, while they demonstrated a response to LPS similar to that of the RA/VD-differentiated cells. Together with the fact that jacalin interacts with CD4, these results provide evidence of the involvement of a CD4 dependent pathway in IL-6 production. J. Leukoc. Biol. 55: 214–220; 1994.
Interleukin-12
Authors: Brunda Michael J
Published: January 2018

Interleukin-12 (IL-12) is a newly characterized cytokine that has a unique heterodimeric structure. It was initially cloned from B lymphoblastoid cell lines, but the majority of IL-12 is produced by macrophages/monocytes following appropriate stimulation. IL-12 can (1) enhance the cytolytic activity of a number of effector cells including T cells, natural killer (NK) cells, lymphokine activated killer (LAK) cells, and macrophages, (2) increase proliferation of activated NK and T cells, (3) induce production of cytokines, such as interferon gamma, (4) stimulate the induction of ThI cells, (5) upregulate a number of cell surface molecules, (6) inhibit IgE secretion, and (7) act as a synergistic factor for hematopoietic stem cells. Based on these potent immunomodulatory activities, IL-12 has been evaluated in several disease models for parasitic infections and malignancies. Marked activity of IL-12 against both Lcishmania and Toxoplasma has been reported. Likewise, antimetastatic and antitumor activity, including tumor regression, has been observed against a number of murine malignancies treated with IL-12 using doses that result in little toxicity. The results suggest that IL-12 may be a useful cytokine for the treatment of a number of diseases. J. Leukoc. Biol. 55: 280–288; 1994.
A method for obtaining and culturing large numbers of purified organ-derived murine endothelial cells
Authors: MacPhee Martin J , Wiltrout Robert H , McCormick Kathryn L , Sayers Thomas J , Pilaro Anne M
Published: January 2018

Fibroblast growth factor 1 (FGF-1)–coated collagen-gelatin sponges were affixed to various tissues to generate vascular beds, in which the vessels originated in the tissue to which the sponges were affixed. Organ-derived endothelium was obtained from vascularized sponges implanted in or on the skin, peritoneal wall, abdominal mesentery, epimysium, spleen, and liver. Collagenase digestion yielded single-cell suspensions that were analyzed by flow cytometry. Approximately 25% of the cells were positive for the endothelial cell (EC) markers MECA-32 and Sca-1 and for uptake of diIAcLDL. Similar results were obtained when sponges were implanted in several different mouse strains, although there was some evidence of heterogeneity in the degree of vascularization and EC recovery. Long-term cultures of high purity were obtained when the ECs were grown on mitomycin C-treated L929 feeder layers, in medium supplemented with cis-hydroxyproline and FGF-1. These cells have been utilized in preliminary studies of T cell-EC binding. Thus we have developed a generalized method for the recovery and culture of organ-derived murine endothelial cells. This technique should greatly improve the feasibility of studies of the interactions between murine endothelial and immune effector cells. J. Leukoc. Biol. 55: 467–475; 1994.
Immunophenotypic and ultrastructural heterogeneity of macrophage differentiation in bone marrow and fetal hematopoiesis of mouse in vitro and in vivo
Authors: Morioka Yuki , Naito Makoto , Sato Tatsuo , Takahashi Kiyoshi
Published: January 2018

The present in vitro study revealed marked differences in immunophenotypic expression and ultrastructure among macrophage colony-stimulating factor (M-CSF)–derived, granulocyte-macrophage colony-stimulating factor (GM-CSF)–derived, and multi-CSF–derived macrophages. M-CSF–derived macrophages were larger and had more markedly differentiated intracellular organelles and more cytoplasmic projections than GM-CSF–or multi-CSF–derived macrophages. By the combined method of ultrastructural peroxidase cytochemistry and immunoelectron microscopy, ER-MP12 was demonstrated mainly on blastic cells; ER-MP20 on promonocytes, monocytes, and immature macrophages; and F4/80 or BM8 on immature and mature macrophages and monocytes. Macrophage heterogeneity was demonstrated to occur at the stage of macrophage precursor cells, and macrophage differentiation was different between bone marrow hematopoiesis and early fetal hematopoiesis. In vivo, F4/80- or BM8-positive (+) macrophages and ER-MP12 (+) cells developed in the yolk sac prior to the appearance of ER-MP20 (+) monocytic cell series. These results imply that CSFs are important factors for the generation of phenotypic heterogeneity of macrophage populations not only in bone marrow but also in fetal hematopoiesis, suggesting that there are different pathways of macrophage differentiation. J. Leukoc. Biol. 55: 642–651; 1994.
P-selectin-dependent leukocyte recruitment and intestinal mucosal injury induced by lactoferrin
Authors: Kurose Iwao , Yamada Tamaki , Wolf Robert , Granger D Neil
Published: January 2018

Plasma concentrations of lactoferrin relevant to an inflammatory response are known to elicit leukocyteendothelial cell adhesion in mesenteric venules. The objectives of this study were (1) to determine whether exogenously administered lactoferrin causes microvascular and mucosal injury in rat intestine and (2) to assess the contribution of adherent leukocytes to a lactoferrinmediated injury process. Mucosal myeloperoxidase (MPO) activity and vascular protein clearance were monitored in the distal intestine of male Sprague-Dawley rats. Macroscopic erosive lesions of the mucosa and increases in mucosal MPO and intestinal vascular protein were observed 2 h following the lactoferrin infusion, results consistent with granulocyte accumulation and microvascular protein leakage. These lactoferrin-induced alterations were significantly attenuated in animals pretreated with a monoclonal antibody (mAb) directed against P-selectin but not by an E-selectin-specific mAb. In another series of experiments, leukocyte adherence/emigration and leakage of fluorescein isothiocyanate (FITC)-labeled albumin were measured in rat mesenteric venules using intravital video microscopy. Lactoferrin elicited increases in both leukocyte adhesion/emigration and albumin extravasation, which were attenuated by mAbs directed against P-selectin but not E-selectin. These observations indicate that (1) the lactoferrin released by activated neutrophils may lead to significant microvascular and mucosal injury or dysfunction and (2) the lactoferrininduced injury is related to P-selectin-mediated adhesion of leukocytes to microvascular endothelium. Our results raise the possibility that neutrophil-derived lactoferrin contributes to the inflammatory response by promoting further granulocyte accumulation and activation and that mAbs to P-selectin may be therapeutically beneficial in inflammatory disorders. J. Leukoc. Biol. 55: 771–777; 1994.
Regulation of polymorphonuclear leukocyte membrane fluidity: effect of cytoskeletal modification
Authors: Wiles Marc E , Dykens James A , Wright Clifford D
Published: January 2018

We previously demonstrated that the f-actin cytoskeleton modulates oxygen radical production associated with polymorphonuclear leukocyte (PMN) oxidative burst activity. Given the close association of the actin and microtubule cytoskeletons with the plasma membrane and the transmembrane location of the PMN NADPH oxidase, it is likely cytoskeletal change may affect PMN membrane responses, such as cellular anisotropy. Changes in PMN membrane fluidity were therefore examined after PMN activation by the chemoattractant N-formyl-1-methionyl-1-leucyl-1-phenylalanine (fMLP) in the presence or absence of phalloidin or cytochalasin B (CB), agents that stabilize and disrupt f-actin, or taxol and vincristine, which stabilize and disrupt microtubules, respectively. Phalloidin and taxol treatment of PMN significantly decreased whereas CB and vincristine significantly increased membrane fluidity. Activation of PMN by fMLP (10-6 M) resulted in a significant increase in membrane fluidity that was attenuated by PMN pretreatment with phalloidin or taxol. CB and vincristine pretreatment of PMN did not alter the fMLP response. These data suggest that stabilization of the f-actin or microtubule cytoskdeton may prevent increases in cellular membrane fluidity associated with PMN activation.—J. Leukoc. Biol. 56: 192–199; 1994.
Biology of the mononuclear phagocyte system of the central nervous system and HIV infection
Authors: Perry V H , Lawson L J , Reid D M
Published: January 2018

Infection of the central nervous system by HIV-1 results in widespread neuropathology and neurological symptoms. The cells infected in the brain belong to the mononuclear phagocyte lineage. We review aspects of the biology of the macrophage populations associated with the central nervous system and consider their distribution, phenotype, and kinetics in relation to HIV pathology. J. Leukoc. Biol. 56: 399–406; 1994.
Interactions between lymphocytes, macrophages, and central nervous system cells
Authors: Couraud Pierre-Olivier
Published: January 2018

Brain has often been considered as an “immunologically privileged organ,” not normally accessible to leukocyte traffic, at least in part because of the presence of the blood-brain barrier, constituted by a specialized microvasculature and surrounding astrocytes, which restricts the exchanges between blood and brain. However, more recent studies have revealed that activated leukocytes can cross into the CNS, at very low levels under normal conditions, in much higher numbers during neuro-pathological disorders like multiple sclerosis or retroviral infection, and, within brain parenchyma, interact with CNS cells. The present review will thus highlight the multidirectional communication network, based on adhesion molecule expression and cytokine production, which appears in such situations between infiltrated leukocytes, brain microvessel endothelial cells, macroglia (including astrocytes and oligodendrocytes), microglial cells and neurons. J. Leukoc. Biol. 56: 407–415; 1994.
Molecular mechanism of interleukin-8 gene expression
Authors: Mukaida Naofumi , Okamoto Shu-ichi , Ishikawa Yuji , Matsushima Kouji
Published: January 2018

A potent leukocyte chemotactic and activating cytokine, interleukin-8 (IL-8), is produced by numerous types of cells in response to inflammatory stimuli. Accumulating evidence indicate that the transcription of IL-8 gene requires the activation of either the combination of NF-xB and AP-1 or that of NF-xB and NF-IL6, depending on the type of cells. Alternatively, the activation of NF-xB is indispensable for IL-8 gene activation in any types of cells examined. On the other hand, an immunosuppressant, FK506, and a glucocorticoid inhibit the gene transcription as well as the production of IL-8. Molecular analyses of IL-8 gene repression by these agents revealed that both affected the activity of the transcription factor(s) bound to the NF-xB site, albeit in different ways, thereby suppressing IL-8 gene transcription. Collectively, IL-8 production seems to be controlled mainly at the activation step of the transcription factor(s) bound to the NF-xB site. J. Leukoc. Biol. 56: 554–558; 1994.
Isolation of antimicrobial peptides from avian heterophils
Authors: Evans Ellen W , Beach Gwen G , Wunderlich John , Harmon Barry G
Published: January 2018

Five bactericidal peptides (chicken heterophil peptides CHP1 and CHP2; turkey heterophil peptides THP1, THP2, and THP3) were purified from avian heterophil granules. All peptides were cationic and rich in cysteine, arginine, and lysine. The complete amino acid sequence, consisting of 39 amino acids, was determined for CHP1. This peptide had a molecular weight of 4481 as determined by mass spectrometry. Partial NH2-terminal amino acid sequences were obtained for the remaining peptides. Both chicken peptides and THP1 shared sequence homology at 22 residues and a cysteine motif which was similar to that of bovine beta-defensins. THP2 and THP3 were homologous to each other but were not homologous to the other three and had a unique cysteine motif. Peptides CHP1, CHP2, and THP1 killed Staphylococcus aureus and Escherichia coli in vitro, whereas THP2 and THP3 killed only S. aureus in vitro. J. Leukoc. Biol. 56: 661–665; 1994.
Kinetics of macrophage subpopulations and expression of monocyte chemoattractant protein-1 (MCP-1) in bleomycin-induced lung injury of rats studied by a novel monoclonal antibody against rat MCP-1
Authors: Sakanashi Yuji , Takeya Motohiro , Yoshimura Teizo , Feng Lili , Morioka Tohru , Takahashi Kiyoshi
Published: January 2018

We investigated the kinetics of macrophage subpopulations and the expression of monocyte chemoattractant protein 1 (MCP-1) in a rat model of bleomycin-induced lung injury. Rat macrophage subpopulations were examined by immunohistochemistry using various anti-rat macrophage monoclonal antibodies (mAbs) and their proliferative capacity by [3H]thymidine (3HTdR) autoradiography. To detect the localization of expressed MCP-1, we generated an mAb against rat MCP-1 for immunohistochemical staining. Expression of MCP-1 messenger RNA (mRNA) was detected by Northern blot hybridization. Shortly after intratracheal instillation of bleomycin, the number of exudate macrophages recognized by mAb TRPM-3 increased in the injured lungs, peaked 3 days later, and decreased thereafter, whereas tissue macrophages identified by mAb ED2 increased slowly and peaked 2 weeks after instillation. Northern blot analysis disclosed that the expression of MCP-1 mRNA in the lung was most prominent 1 day after instillation and declined thereafter, preceding the numerical change of the TRPM-3-positive exudate macrophages. Immunohistochemistry with anti-rat MCP-1 revealed that the main sources of MCP-1 production were alveolar and interstitial macrophages and polymorphonuclear leukocytes. Based on these results, MCP-1 produced by polymorphonuclear leukocytes and by alveolar and interstitial macrophages is thought to induce the infiltration of blood monocytes, and infiltrated exudate macrophages produce MCP-1 to enhance subsequent accumulation of macrophages. In contrast, the expression of MCP-1 did not correlate with the numerical changes of the ED2-positive macrophages. J. Leukoc. Biol. 56: 741–750; 1994.
Enhancement of murine serum amyloid A3 mRNA expression by glucocorticoids and its regulation by cytokines
Authors: Ishida Tetsuya , Matsuura Keiko , Setoguchi Mihoko , Higuchi Yasunori , Yamamoto Shunsuke
Published: January 2018

Macrophages are regulated by hormones, cytokines, and other substances. We examined the effects of glucocorticoids (GC) on serum amyloid A (SAA) mRNA expression using an antisense SAA3 probe, and found that dexamethasone (DEX) and triamcinolone (TC) increased SAA3 mRNA expression by macrophage cell lines in a time- and concentration-dependent manner. Both an RNA polymerase II antagonist, α-amanitin, and a specific GC antagonist, RU38486, inhibited the enhancement of SAA3 mRNA expression by DEX. These results show that GC lead to enhanced SAA3 mRNA transcription. Nuclear run-on experiments supported these results. Enhanced expression of SAA3 mRNA by DEX was accompanied by production of SAA3 protein. Interferon-γ (IFN-γ) alone showed any effect on SAA3 mRNA expression. Enhanced SAA3 expression by DEX was inhibited by treatment with IFN-γ in a dose-dependent manner. Either transforming growth factor (TGF)-β1 or interleukin (IL)-4 alone showed no effect on SAA3 mRNA expression, but suppressed DEX-induced SAA3 expression. The timing of the effects of IFN-γ and TGF-βl on DEX- induced SAA3 expression differed: IFN-γ showed its effect between 30 h before and 18 h after DEX administration, whereas TGF-β1 showed an effect when administered concomitantly with DEX and in the late stages after DEX administration. IL-4 mildly suppressed DEX-induced SAA3 expression when given 12 h before and after DEX administration. J. Leukoc. Biol. 56: 797–806; 1994.
Comparative ultrastructure and immunolabeling of MHC-II antigens of alveolar macrophages obtained from patients with paracoccidioidomycosis and other lung diseases
Authors: Bretañ;a Antonio , Goihman-Yahr Mauricio , Tapia Felix J , Istúriz Guillermo , Viloria Nora , Carrasquero Mercedes , Saavedra Nelly , de Albornoz María C , Pereira José , de Román Ana , de Gómez Maria H
Published: January 2018

Samples of alveolar macrophages (AM) obtained by bronchoalveolar lavage from patients with either paracoccidioidomycosis, silicosis, sarcoidosis, or allergic alveolitis were investigated by electron microscopy and immunocytochemistry to compare cellular ultrastructure and expression of MHC-II antigens in the AM cell surface. All samples of AM obtained from patients with these pathologies showed heterogeneous structural features. Although, this morphological diversity is also present in AM of healthy donors, our observations seem to indicate that in the diseases studied this morphofunctional diversity is associated with additional ultrastructural characteristics inherent to each disease. In paracoccidioidomycosis the proportion of vacuolated macrophages is significantly lower than in other diseases; this might indicate that in paracoccidioidomycosis the proportion of activated AM is smaller. We observed significant differences in the expression of MHC-II antigens. Silicosis, sarcoidosis, and allergic alveolitis do not differ significantly in the quantity of immunolabeled AM or in the distribution of the label. The percentage of AM from paracoccidioidomycosis that exhibit the MHC-II molecule is very low with poor immunolabeling. In this disease the low expression of the MHC-II molecule could be related to a decrease of the antigen presenting function by AM. J. Leukoc. Biol. 57: 101–109; 1995.
Inactivation of interleukin-8 by aminopeptidase N (CD13)
Authors: Kanayama Naohiro , Kajiwara Yayoi , Goto Junko , El Maradny Emad , Maehara Kayoko , Andou Katuaki , Terao Toshihiko
Published: January 2018

Aminopeptidase (APN) was found to degrade interleukin-8 (IL-8) and inactivate its chemotactic activity. The chemotactic activity of IL-8 was decreased by APN or neutrophil plasma membranes dose- and time-dependently. The chemotactic activity was not inactivated in the presence of bestatin or WM15 monoclonal antibody. The expression of IL-8 was measured by flow cytometry. On lipopolysaccharide (LPS) stimulation, IL-8 expression increased for 60 min and then decreased markedly. In contrast, on treatment with LPS and bestatin, the expression of IL-8 increased continuously for at least 120 min. These results suggest that the expression and release of IL-8 from phagocytic cells are regulated by the proteolytic effect of APN on IL-8. J. Leukoc. Biol. 57: 129–134; 1995.
Mycoplasma stimulates the production of oxidative radicals by murine peritoneal macrophages
Authors: Avron Ann , Gallily Ruth
Published: January 2018

Mycoplasmas and mycoplasma membranes have been shown to induce the production of inflammatory cytokines, including tumor necrosis factor α and interleukin-6, as well as nitric oxide, by mouse macrophages and rat brain astrocytes. Luminol-enhanced chemiluminescence was used as a sensitive method to show that Mycoplasma capricolum membranes induce mouse peritoneal macrophages to produce reactive oxygen radicals. Coincubation of the mycoplasma with a secondary stimulus, namely macrophage-activating factor or interferon-γ, increased the chemiluminescence. The augmentation was abolished by the nitric oxide synthase inhibitor NG-methyl-l-arginine, indicating the involvement of nitric oxide. The coproduction of superoxide and nitric oxide by the same cell allows the formation of the powerful oxidant peroxynitrite, which could be responsible for the increased chemiluminescence. Induction of oxidizing radicals by mycoplasmas may contribute to the clinical pathology seen in mycoplasma infections. J. Leukoc. Biol. 57: 264–268; 1995.
Activation of multiple protein kinases induced by cross-linking of FcγRII in human neutrophils
Authors: Liang Li , Huang Chi-Kuang
Published: January 2018

Several neutrophil protein kinases that undergo changes in activity during FCγRII activation have been investigated. These kinases include calcium/calmodulin-dependent protein kinase II (CAMPKII), mitogen-activated protein kinase (MAPK), and histone H4 protein kinase (PKH4). They are rapidly and transiently activated in a dose-dependent manner by the cross-linking of FCγRII. The activation of CAMPKII but neither PKH4 nor MAPK was inhibited by treating the cells with either a tyrosine kinase inhibitor, genistein, or an intracellular calcium chelator, BAPTA/AM. The superoxide production induced by cross-linking FCγRII can be inhibited partially by various protein kinase inhibitors: 33% by protein kinase C inhibitor calphostin C, 30% by CAMPKII inhibitor KN-62, and 62% by tyrosine kinase inhibitor genistein. These results indicate that cross-linking of FCγRII induces multiple signaling pathways that lead to the activation of various protein kinases. The activation of these kinases may be involved directly or indirectly in the regulation of superoxide production. J. Leukoc. Biol. 57: 326–331; 1995.
Evidence for LFA-1/ICAM-1 dependent stimulation of protein tyrosine phosphorylation in human B lymphoid cell lines during homotypic adhesion
Authors: Wang Shirley C-T , Kanner Steven B , Ledbetter Jeffrey A , Gupta Shalini , Kumar Gita , Nel André E
Published: January 2018

JK32.1 and SKW6.4 are Epstein-Barr virus (EBV)-positive human B cell lines that undergo spontaneous, lymphocyte function-associated antigen 1 (LFA-1) dependent homotypic adhesion in culture. This process is associated with induction of tyrosine phosphoproteins of molecular mass 90, 106, and 120 kDa and could be reproduced when these cells were centrifugationally aggregated. Antibodies to the β  2 (CD18) chain of LFA-1 interfered with induction of p120, p106, and p90 during cellular aggregation. Response induction was abrogated when cells were incubated with protein tyrosine kinase (PTK) inhibitors (erbstatin, genistein, and geldanomycin) or cytochalasin B prior to aggregation. An in vitro kinase assay did not reveal activation of focal adhesion kinase. Although the role of LFA-1-dependent tyrosine phosphorylation in B cells is uncertain, patients with the leukocyte adhesion defect (LAD) exhibit humoral abnormalities. Moreover, aggregation did not induce specific tyrosine phosphoproteins in an EBV-transformed B cell line from a LAD patient. These results suggest that an LFA-1-dependent PTK pathway may play an important role in human B cell function. J. Leukoc. Biol. 57: 343–351; 1995.
Effects of oxidized LDL on mononuclear phagocytes: inhibition of induction of four inflammatory cytokine gene RNAs, release of NO, and cytolysis of tumor cells
Authors: Thai S-F , Lewis J G , Williams R B , Johnson S P , Adams D O
Published: January 2018

A critical step in development of atherosclerosis is the interaction of oxidized low-density lipoprotein (LDL) with mononuclear phagocytes. Oxidized LDL, as well as acetyl-LDL, is rapidly taken up into macrophages via a family of scavenger receptors. We report that macrophages treated with oxidized LDL have markedly lower levels of mRNA specific for the genes MCP-1, TNF-α, IL-1α, and KC as measured by Northern blot analyses of lipopolysaccharide (LPS)-stimulated macrophages. By contrast, acetyl-LDL does not inhibit these genes at the doses at which oxidized-LDL is effective. Similar effects are observed whether the LDL is oxidized in the presence of Cu2+ or of Fe2+. Such inhibition also occurs when maleylated bovine serum albumin (BSA), which also clears by one or more scavenger receptors on macrophages, is used as the stimulant. Fe2+ or Cu2+ oxidized LDL inhibits release of nitric oxide when triggered by LPS and direct cytolysis of tumor cells when triggered by maleylated BSA or LPS. Taken together, the data presented indicate that oxidized LDL inhibits induction of several important gene RNAs as well as functional markers that characterize the development of inflammatory and fully activated macrophages. J. Leukoc. Biol. 57: 427–433; 1995.
Na+-H+ exchange in resident alveolar macrophages: activation by osmotic cell shrinkage
Authors: Heming Thomas A , Bidani Akhil
Published: January 2018

Intracellular pH (pH;) homeostasis in resident alveolar macrophages (mφ) under nominally CO2-free conditions is mediated primarily by the activity of plasmalemmal H+-ATPase, The mφ also possess an Na+-H+ exchanger (NHE) but this mechanism has no de tectable role in pHi regulation in the physiologic range. To further explore the physiological significance of the NHE in this cell type, resident alveolar mφ from rabbits were subjected to a hyperosmotic challenge (620 mOsm/kg) in the nominal absence of C02-HCO3-. Os motic cell shrinkage was accompanied by an amiloridesensitive increase in baseline pHi The NHE-mediated rate of pH; recovery from intracellular acid loads also in creased under hyperosmotic conditions. Cell shrinkage caused an alkaline shift in the pHi set point of the NHE without altering the exchanger’s affinity for extracellular Na+. The results indicate that Na+-H+ exchange in resi dent alveolar mφ is activated by osmotic cell shrinkage and imply that the NHE may be involved in volume regulatory responses of the cell. J. Leukoc. Biol. 57: 609–616; 1995.
Tumoricidal response of liver macrophages isolated from rats bearing liver metastases of colon adenocarcinoma
Authors: Thomas C , Nijenhuis A M , Dontje B , Daemen T , Scherphof G L
Published: January 2018

Iniraportal Inoculation of CC531 adenocarcinoma cells into syngeneic rats causes an increase of liver macrophage cell number but not of major histocompati bility complex class II antigen expression. On day 1 after inoculation of 105 CC531 cells, a fixed number of isolated liver macrophages lysed significantly more target cells in vitro than did control cells. This effect was still present after 4 weeks, A 10-fold higher initial tumor dose sig nificantly suppressed the macrophage response during the first 2 weeks. In contrast to tumoricidal activity induced by lipopolysaccharide in vitro, the tumoricidal response following in vivo challenge with tumor cells appeared not closcly related to the production of reactive nitrogen in termediates, as in the latter case it was not abrogated in the presence of nitric oxide synthase inhibitor. Further more, the liver macrophage population appeared not fully activated after tumor inoculation as lipopolysaccharide further increased tumoricidal activity in vitro. The ob served numerical and functional response of liver macro phages to intraportally inoculated tumor cells points at an important role of these cells in aspecific immune reac tivity aimed at the reduction of local tumor growth. Re sults suggest that mechanistic differences exist between macrophage tumoricidal activity induced by tumor cells as compared with lipopolysaccharide. J. Leukoc. Biol. 57: 617–623; 1995.
Structure-activity relationships of chemokines
Authors: Clark-Lewis Ian , Kim Key-Sun , Rajarathnam Krishnakumar , Gong Jiang-Hong , Dewald Beatrice , Moser Bernhard , Baggiolini Marco , Sykes Brian D
Published: January 2018

Structural analysis of chemokines has revealed that the α/β structural-fold is highly conserved among both the CXC and CC chemokine classes. Although dimerization and aggregation is often observed, the chemokines function as monomers. The critical receptor binding regions are in the NH2-terminal 20 residues of the protein and are the least ordered in solution. The flexible NH2-terminal region is the most critical receptor binding site and a second site also exists in the loop that follows the two disulfides. The well-ordered regions are not directly involved in receptor binding but, along with the disulfides, they provide a scaffold that determines the conformation of the sites that are critical for receptor binding. These general requirements for function are common to all the chemokines. For the CC chemokines, receptor activation and receptor binding regions are separate within the 10 residue NH2-terminal region. This has allowed identification of high affinity analogs that do not activate the receptor and are potent antagonists. J. Leukoc. Biol. 57: 703–711; 1995.
Interleukin-5 and its receptor: a drug target for eosinophilia associated with chronic allergic disease
Authors: Devos René , Plaetinck Geert , Comelis Sigrid , Guisez Yves , Van der Heyden José , Tavemier Jan
Published: January 2018

A characteristic feature of chronic allergic diseases such as asthma is the increase in eosinophil numbers in the inflamed tissue. In light of its specificity for the development of eosinophils, interleukin-5 (IL-5) is considered the most important cytokine involved in the regulation of eosinophilia. Hence, an antagonist for IL-5 activity is a new target for drug discovery programs. We have examined the opportunity for both a random and a rational approach for the identification of such an antagonist. The elucidation of the structure of IL-5 and the initial structure/function analysis of the ligand/receptor complex constitute a first step towards the design of antagonistic compounds. The identification of a small compound by random screening able to inhibit the IL-5/IL-5 receptor interaction indicated an important domain in the receptor. We examine here protein-based IL-5 antagonists, such as IL-5-muteins, soluble IL-5 receptor constructs, and monoclonal antibodies, for their potential as IL-5/IL-5 receptor antagonists, and the use of a murine model of eosinophil airway inflammation for their evaluation. J. Leukoc. Biol. 57: 813–819; 1995.
Cytokine induction by the immunomodulators imiquimod and S-27609
Authors: Testerman Traci L , Gerster John F , Imbertson Linda M , Reiter Michael J , Miller Richard L , Gibson Sheila J , Wagner Tamara L , Tomai Mark A
Published: January 2018

Imiquimod (R-837, S-26308) and the analogue S-27609 were evaluated for cytokine induction in human blood cells. Both compounds induced interferon-α (EFN), tumor necrosis factor-α (TNF), interleukin (IL)-1β, and EL-6 with S-27609 being 5 to 10 times more potent. Imiquimod and S-27609 also induced IL-1α, IL-1 receptor antagonist, IL-10, granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte CSF (G-CSF), and macrophage inflammatory protein-1α. The profile of cytokines induced by imiquimod and S-27609 was different from those seen with lipopolysaccharide and polyinosinic-polycytidylic acid. Kinetic studies with both imiquimod and S-27609 revealed induction of cytokines as early as 1-4 h after stimulation. Although most of the cytokines produced by S-27609 were secreted, significant concentrations of IL-1α and BL-1β remained intracellular. Monocytes were largely responsible for the cytokines produced. Finally, S-27609-induced mRNA expression for TNF, IFN, and IL-8, and this induction did not require protein synthesis. Taken together, these studies extend previous findings by showing induction of additional cytokines and providing insight into the mechanism of cytokine induction by these molecules.
Histamine enhances granulocyte-macrophage colony-stimulating factor and interleukin-6 production by human peripheral blood mononuclear cells
Authors: Mor Shlomith , Nagler Arnon , Barak Vivian , Handzel Zeev T , Geller-Bernstein Carmi , Fabian Ina
Published: January 2018

The effect of histamine on the production of cytokines by subpopulations of mononuclear cells was studied. A 3.5-fold increase in the number of myeloid colony-forming units (CFU-C) was observed when bone marrow cells were cultured in the presence of conditioned medium prepared from nonadherent mononuclear cells cultured with 10−4 M histamine (CM-histamine) compared with phosphate-buffered saline (CM-PBS). Using ELISA and radioimmunoassay kits, histamine was found to enhance the production of GM-CSF (9.6-fold) and IL-6 (8.2-fold) by mononuclear cells but not by nonadherent cells or large granular lymphocytes. Anti-GM-CSF and anti-IL-6 antibodies markedly blocked cytokine activity in CM-PBS, whereas the blocking effect in CM-histamine was moderate, indicating enhanced GM-CSF and IL-6 activity in CM-histamine. No GM-CSF or IL-6 levels could be detected in CM-histamine or CM-PBS prepared from CD3+, CD4+, or CD8+ lymphocytes. Preincubation of CM-histamine with H1 and H2 receptor antagonists resulted in complete blocking of the histamine-enhanced colony-stimulating activity. We conclude that histamine is able to activate human mononuclear cells to generate cytokines such as GM-CSF and IL-6 via H1 and H2 receptors.
Unique patterns of regulation of nitric oxide production in fibroblasts
Authors: Lavnikova Natasha , Laskin Debra L
Published: January 2018

The pathways regulating rat and mouse embryonic and lung fibroblast nitric oxide production were analyzed in an attempt to evaluate the potential role of these cells in nonspecific host defense and inflammation. Interleukin-1β (IL-1β) was found to be the strongest single activator in all types of fibroblasts examined. In addition, lipopolysaccharide (LPS) was synergistic with IL-1β or tumor necrosis factor-α (TNF-α) in induction of nitric oxide synthesis. These patterns of responsiveness are not observed in macrophages and may be significant in initiation of early host defense processes, before specific interferon-γ (IFN-γ)–mediated immune responses have become operative. Rat and mouse fibroblasts were also found to produce nitric oxide when primed with IFN-γ and simultaneously treated with IL-1, TNF-α, or LPS. The doses of IFN-γ effective in priming fibroblasts for nitric oxide production were as low as 1-10 U/ml. Furthermore, effective triggering doses of LPS, TNF-α, and IL-1 were 10 ng/ml, 100 U/ml, and 0.2 ng/ml, respectively. These results demonstrate that fibroblasts are activated more readily to produce nitric oxide than interstitial macrophages and may be the major source of this mediator in tissues. Immunohistochemical studies demonstrated that fibroblasts are heterogeneous with respect to inducible nitric oxide synthase expression with the majority of cells not involved in the response. Fibroblasts were also found to be distinct from macrophages in their sensitivity to the suppressive effects of Transforming growth factor-β, which in fibroblasts inhibited both IFN-γ plus LPS–and IFN-γ plus TNF-α-induced nitric oxide production. At the stage of growth crisis, a dramatic increase in nitric oxide production was observed in rat fibroblasts in response to IFN-γ or TNF-α that may be directly correlated with cellular senescence. Taken together, our data suggest that mouse and rat fibroblasts are potential effectors in both IFN-γ-dependent and -independent nitric oxide-mediated processes and that the patterns regulating nitric oxide metabolism in these cells are distinct from those of macrophages.
Dendritic cells and the replication of HIV-1
Authors: Cameron P , Pope M , Granelli-Piperno A , Steinman R M
Published: January 2018

Dendritic cells (DCs) are a distinct lineage of white cells that arise from CD34+ progenitors in the bone marrow. DCs exhibit many specializations that lead to efficient antigen capture and presentation to T cells, both CD4+ helpers and CD8+ killers. In several human tissues, DCs express the CD4 receptor for HIV-1. Some early reports described the explosive infection of blood-derived DCs by HIV-1 and a severe compromise of their presenting function. In contrast, other studies described active HIV-1 replication when DCs were interacting with CD4+ T cells. This productive infection could begin with a low viral burden in DCs but required that the DCs retain their normal binding and stimulatory function for T cells. In this review we first summarize those features of the DC system that seem pertinent to HIV-1 infection. Then we consider the current literature on the interaction of HIV-1 with DCs, from several different tissues, in HIV-1-infected patients or following challenge with HIV-1 in vitro. The literature leads to the hypothesis that HIV-1 infection is a battleground in which DCs could be leading both of the armies, the aggressor that promotes HIV-1 replication from relatively small numbers of infected cells and the defender that mediates T cell-dependent resistance.