bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanisms generating functionally heterogeneous macrophages: chaos revisited
Authors: Rutherford Mark S , Witsell Alice , Schook Lawrence B 
Published: January 2018

Abstract
Macrophage populations exhibit a wide range of antigenic and functional phenotypes, including cytokine production, response to immunomodulatory stimuli, and clearance of pathogens. The expanding clinical exploitation of recombinant growth factors and cytokines with the potential to regulate the production and function of peripheral macrophage populations necessitates an increased understanding of the mechanisms by which functionally distinct macrophage populations arise as well as the ramifications of macrophage heterogeneity. The present review summarizes recent data which supports multiple mechanisms by which heterogeneous macrophage populations arise: 1) differential signals experienced within diverse tissue microenvironments; 2) developmentally-staged expression of specific functions; 3) clonal variation of myeloid progenitor cells; and 4) alternate hematopoietic stimulation. These data show that the above processes are not mutally exclusive and that each likely contributes to the observed heterogeneity of peripheral macrophage populations. J. Leukoc. Biol. 53: 602–618; 1993.
Phospholipase C and phospholipase D are activated independently of each other in chemotactic peptide-stimulated human neutrophils
Authors: Mullmann Theodore J , Cheewatrakoolpong Boonlert , Anthes John C , Siegel Marvin I , Egan Robert W , Billah M Motasim 
Published: January 2018

Abstract
When cytochalasin B-treated neutrophils were stimulated with fMet-Leu-Phe (fMLP) in the presence of Ca2+, phospholipase C (PLC) activity, as measured by inositol-1,4,5-trisphosphate (IP3) formation, preceded phospholipase D (PLD)-catalyzed breakdown of choline- containing phosphoglycerides to form choline and dirady 1-sn -glycero-3-phosphate (phosphatidic acid), suggesting a possible link between PLC and PLD. However, in the absence of cytochalasin B or extracellular Ca2+, PLC was fully activated by fMLP with minimal activation of PLD, indicating that PLC activation alone is not sufficient for PLD activation. Full activation of PLD by fMLP required the simultaneous presence of both Ca2+ and cytochalasin B, a condition that caused no further enhancement of PLC. This result suggests that PLD products are not involved in the regulation of PLC activation. Furthermore, under conditions of complete inhibition of PLC by phorbol 12-myristate 13-acetate (PMA), there was no inhibition of PLD, showing that fMLP can activate PLD in the absence of PLC. Treatment of intact neutrophils with pertussis toxin inhibited both PLC and PLD, with PLC inhibition occurring at lower concentrations than PLD inhibition. These differential effects of pertussis toxin and the observed lack of inhibition of fMLP-stimulated PLD by PMA, which is believed to inactivate G-proteins involved in PLC activation, imply that PLC and PLD are linked to fMLP receptors through distinct G-proteins. Taken together, these observations suggests that, in fMLP-stimulated neutrophils, PLC and PLD are activated through independent mechanisms. J. Leukoc. Biol. 53: 630–635; 1993.
Stimulation of the bactericidal activity of polymorphonuclear leukocytes by manganese
Authors: Klebanoff Seymour J , Schlechte Kristie G , Waltersdorph Ann M 
Published: January 2018

Abstract
An antioxidant effect of manganese (Mn) complexes due to the scavenging of the superoxide anion (Of) or to the decomposition of hydrogen peroxide (H2O2) has been described. We report here that Mn also can exert a prooxidant effect under certain experimental conditions. Thus Mn2+ in phosphate buffer increased the bactericidal effect of phorbol myristate acetate-stimulated polymorphonuclear leukocytes (PMNs) on extracellular Escherichia coli. This effect was inhibited by azide, catalase, and a decrease in chloride concentration and was not observed when normal PMNs were replaced by those of patients with chronic granulomatous disease or myeloperoxidase (MPO) deficiency. Mn2+ could be replaced by Mn3+ or by superoxide dismutase (SOD). These findings suggest that Mn (or SOD), by increasing the conversion of Of to H2O2, can increase the activity of the MPO-H2O2-chloride antimicrobial system released by stimulated PMNs. J. Leukoc. Biol. 53: 666–672; 1993.
Chemotactic peptide–induced cytoplasmic pH changes in incubated human monocytes
Authors: Bernardo John , Brennan Lisa , Brink Holly F , Ortiz Maria F , Newburger Peter E , Simons Elizabeth R 
Published: January 2018

Abstract
Stimulation of phagocytic leukocytes with chemotactic factors results in transient acidification, followed by alkalinization of the cytosol. Human monocytes are known to alter their functional responses to the chemotactic peptide N-formylmethionyl-leucyl-phenylalanine (fMLP) in a complex fashion as they mature in vitro to macrophages. To examine the evolution of the cytoplasmic pH (pHi) response of monocytes to fMLP as they mature into macrophages, we incubated cells for 0, 24, 48, and 96 h (Medium-199 + 10% fetal bovine serum; 37°C) and examined pHi using the fluorescent probe 2′, 7′-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF; 1 μΜ) and a Perkin-Elmer 650/10 spectrofluorimeter (λem = 530 nm, λ_ex = 500, 450 nm) as previously described. The resting pH; of fresh (0 h) monocytes was 7.07 ± 0.16 (SD) and was unchanged after incubation for 24, 48, or 96 h (7.09, 7.11, 7.05, respectively). Cells exhibited an fMLP dose-dependent cytoplasmic acidification, with maximal δpHi occurring 30-60 s after exposure to 10−7 M fMLP. The response to fMLP did not change with the duration of incubation and, as with neutrophils, cytoplasmic realkalinization was blocked by dimethyl- amiloride (20 μΜ). Incubation with 2-deoxyglucose (10 min, 5 mM), sufficient to inhibit by more than 90% the formyl peptide-stimulated superoxide generation by monocytes, slowed fMLP-induced acidification and abrogated the alkalinization. In addition, monocytes isolated from the blood of a patient with X-linked chronic granulomatous disease (CGD) underwent fMLP-induced acidification that was unmasked further by coincubation with di- methylamiloride, in a manner quantitatively similar to that of normal monocytes, despite the inability of the CGD cells to produce superoxide. The chemotactic factor-induced cytoplasmic pH responses of mono- cytes/macrophages remained constant as the cells matured in vitro and exhibited a dimethylamiloride-independent acidification and dependent alkalinization, as did the response in neutrophils. The cytoplasmic acidification of these cells thus did not correlate with the cells’ production of superoxide and with the concomitant hexose monophosphate shunt activation, as has been suggested for other leukocyte types. J. Leukoc. Biol. 53: 673–678; 1993.
Recombinant bovine GM-CSF primes superoxide production but not degranulation induced by recombinant bovine interleukin-1β in bovine neutrophils
Authors: Tao Weng , Dougherty; Ruth , Johnston Paul , Pickett Walter 
Published: January 2018

Abstract
Bovine neutrophil activation, superoxide production, and β-glucosaminadase release induced by various biological stimuli were examined. Plateletactivating factor (PAF) and recombinant bovine interleukin-1 β (r-BoIL-1β) induced superoxide production and β-glucosaminadase release in bovine neutrophils. When these two responses were compared, the dose requirement for maximum activation was similar for PAF (1 × 10−6 M). However, the concentration of r-BoIL-Ι β required for the maximum degranulation (2.5 × 10−7 M) was 100-fold higher than that for the maximum superoxide production (2.5 × 10-9 M). Furthermore, pretreatment of cells with recombinant bovine granulocyte- macrophage colony-stimulating factor (r-BoGM-CSF) enhanced both superoxide production and β -glucosaminidase release induced by PAF. In contrast, whereas superoxide production induced by r-BoIL-1β was enhanced by r- BoGM-CSF priming, β -glucosaminidase release induced by r-BoIL-lβ was significantly reduced by pretreatment with r-BoGM-CSF. CL 184,005, a PAF antagonist, inhibited PAF-induced glucosaminidase release and superoxide production but did not inhibit r-BoIL-lβ -in- duced superoxide production and degranulation. In addition, it did not inhibit the priming effect of r-BoGM- GSF on r-BoIL-lβ -induced superoxide production. These results suggest that (1) PAF and r-BoIL-1β activate bovine neutrophils by different mechanisms, (2) r-BoGM-CSF primes superoxide production and degranulation induced by PAF, (3) r-BoGM-CSF primes superoxide production but not degranulation induced by r-BoIL-lβ, and (4) the priming effect of r-BoGM-CSF is not mediated by PAF. J. Leukoc. Biol. 53: 679–689; 1993.
Lipopolysaccharide-induced cytokine production and mortality in mice treated with Corynebacterium parvum
Authors: Smith Sidney R , Calzetta Angela , Bankowski Jennifer , Kenworthy-Bott Lynne , Terminelli Carol 
Published: January 2018

Abstract
Tumor necrosis factor a (TNF-α) has been shown to be an important mediator of the lethal effects of endotoxin in several experimental models of septic shock. However, studies with a recombinant human interleukin-1 (IL-1) receptor antagonist protein (IL-lra) suggest a role for IL-1 as a mediator of septic shock as well. In the present study, we show that mice treated in vivo with Corynebacterium parvum are primed for the production of interferon-γ (IFN-γ) and exhibit an enhanced capacity to produce serum IL-Ια, TNF-a, and IL-6 when challenged intravenously with lipopolysaccharide (LPS). The majority of C. parvum -treated mice die within 24 h of an LPS challenge. Pretreatment with a rat antimouse TNF-α monoclonal antibody (mAb) protected 90% of the animals against the lethal endotoxin challenge, while an anti-IFN-γ mAb gave approximately 75% protection. The anti-IFN-7fgamma; mAb also caused a reduction in LPS- induced serum TNF-α and IL-Ια. Anti-IL-la, anti- IL-1β, and anti-IL-6 neutralizing mAb did not protect against lethality when administered to mice prior to the LPS challenge. These results indicate that TNF-α and IFN-γ are major mediators of endotoxin shock in C. parvum-treated mice. The results further suggest that the IFN-γ produced by C. parvum-primed mice in response to an LPS challenge serves as a stimulus for enhanced production of TNF-α and IL-Ια. These findings are consistent with an increasing body of evidence suggesting a major role for IFN-γ in lethal endotoxemia.
Asbestos-induced injury to cultured human pulmonary epithelial-like cells: role of neutrophil elastase
Authors: Kamp David W , Dunne Moyra , Dykewicz Mark S , Sbalchiero Jane S , Weitzman Sigmund A , Dunn Marc M 
Published: January 2018

Abstract
The mechanisms responsible for asbestos- induced pulmonary epithelial cell cytotoxicity, especially oxidant-independent mechanisms, are not established. We determined whether human polymorphonuclear leukocyte (PMN) proteases contribute to asbestos-induced damage to human pulmonary epithelial-like cells (PECs) assessed using an in vitro chromium-51 release assay. Serine antiproteases, phenylmethylsulfonyl fluoride and αι -antitrypsin, each ameliorated PEC injury induced by amosite asbestos and PMNs. A role for a specific proteinase, human neutrophil elastase (HNE), is supported by the facts that (1) asbestos increased HNE release assessed by an enzyme-linked immunosorbent assay technique (1.7 ± 0.5 vs. 2.8 ± 0.5 μg/ml; P &lt; .025), (2) purified HNE or porcine pancreatic elastase (PPE) each alone caused PEC detachment, (3) asbestos plus either HNE or PPE caused PEC lysis similar to that mediated by asbestos and PMNs, and (4) cationic agents released from PMNs were unlikely to be involved because polyanions did not ameliorate injury resulting from asbestos and PMNs. Compared to elastase, cathepsin G caused less PEC detachment and negligible augmentation in asbestos- induced PEC lysis. Asbestos increased the association of 125I-labeled elastase with PECs nearly 50-fold compared with PPE alone (14.4% vs. 0.3%, respectively; P &lt; .01) and nearly 10-fold compared with another particle, opsonized zymosan. We conclude that PMN-derived proteases, especially elastase, may contribute to asbestos- induced lung damage by augmenting pulmonary epithelial cell injury.
Suppressive effect of interleukin-4 on the differentiation of M1 and HL60 myeloid leukemic cells
Authors: Yamashita Uki , Tanaka Yoshiya , Shirakawa Fumihiko 
Published: January 2018

Abstract
Abstract: The effect of interleukin-4 (IL-4) on the proliferation and differentiation of myeloid leukemic cell ines was studied in vitro. A culture of murine myeloid cell line, Ml, with lipopolysaccharide (LPS) from Escherichia coli, induced differentiation into macrophages that expressed Fc receptors and phagocytic ac- ivity. IL-4 did not induce the differentiation of Ml cells put inhibited the differentiation of Ml cells induced with LPS. On the other hand, LPS arrested the proliferation of Ml cells. IL-4 had no effect on the proliferation of Ml cells but restored the LPS-induced arrest of the proliferation of Ml cells. IL-1, IL-6 and tumor necrosis factor a (TNF-α) also induced the differentiation of Ml cells into macrophages and arrested proliferation. IL-4 suppressed the IL-1-, IL-6-, and TNF-induced differentiation of Ml cells and restored the arrested proliferation with IL-1, IL-6, and TNF. Similar results were obtained with human myeloid cell line HL60. These results suggest that IL-4 has a suppressive effect on the differentiation of myeloid cells into macrophages.
Immune changes during long-duration missions
Authors: Konstantinova Irena V , Rykova Marina P , Lesnyak Andrei T , Antropova Eugenia A 
Published: January 2018

Abstract
Immune changes during space flights in excess of two weeks have been almost exclusively studied by Russian investigators. Most of these studies have compared postflight values with those obtained before flight. In a very few cases, analyses have also been attempted during flight or with samples collected during flight. Studies of cosmonauts during spaceflight have shown that IgG levels were unchanged, whereas IgA and IgM levels were sometimes increased. Additionally, inflight delayed type hypersensitivity testing demonstrated a decrease below the warning level in 1/3 of the cosmonauts tested. Pre- vs. postflight analyses have often revealed a postflight decrease in: PHA-triggered lymphocyte blast transformation; the proliferation index of T-lymphocytes in the xenogeneic graft versus host reaction; the mitogen- induced production of interleukin-2; the presence of certain leukocyte sub sets; and cytotoxic activity of natural killer cells. Other factors that either did not change, or changed in an apparently random manner after flight included: production of α and γ interferon; autoimmune tests; and globulin classes.
Antibodies to macrophage stimulating protein (MSP): specificity, epitope interactions, and immunoassay of MSP in human serum
Authors: Wang Ming-Hai , Skeel Alison , Yoshimura Teizo , Copeland Terry D , Sakaguchi Kazuyasu , Leonard Edward J 
Published: January 2018

Abstract
Abstract: Macrophage stimulating protein (MSP) is a member of a family of proteins characterized by a triple disulfide loop structure (kringle). We developed antibodies to human MSP for detection in Western blots, quantification in biological fluids, and neutralization of activity. Immunogens included native MSP, reduced and alkylated α and β chains, and peptides of MSP regions with minimal sequence similarity to other kringle proteins. We found three antibody categories based on interaction with the following types of epitope: primary sequence, discontinuous (dependent on disulfide bonds), and cryptic (not exposed in native MSP). None of the antibodies reacted with related kringle proteins. A specific sandwich ELISA was developed for measuring human MSP. The mean serum concentration was 4 nM. Serum MSP did not increase over a 24-h period in response to intravenous lipopolysaccharide, indicating that MSP is not an acute phase protein. These findings are consistent with the hypothesis that regulation of MSP activity is by conversion of pro-MSP to MSP rather than by rapid changes in rates of synthesis.
Macrophage-tumor cell associations: a factor in metastasis of breast cancer?
Authors: van Netten J P , Ashmead B J , Parker R L , Thornton I G , Fletcher C , Cavers D , Coy P , Brigden M L 
Published: January 2018

Abstract
In human breast carcinomas tumor cells and macrophages are often proximal. We previously reported on the relationship between tumor cell growth and macrophage concentration and report here on the possible involvement of macrophages in the metastatic process. We hypothesize that during the initial stages of metastasis, tumor cells are likely to encounter macrophages and form aggregates. Using a cell culture method that encourages cellular interactions, we found aggregates involving macrophages. Macrophages partly or completely surround other cell types without any apparent ill effect. Units involving macrophages and tumor cells would possess many properties necessary for invasion, which is a normal process for macrophages. Properties such as motility and production of specific enzymes necessary to traverse the extracellular matrix, basement membrane, and endothelial cell barriers may provide an advantage for tumor cells. Physical support and protection from immune recognition during transport of the tumor cell through the vascular system may also be enhanced, and paracrine growth stimulation and angiogenic activity may be provided at the new metastatic site. Verification of these observations in vivo could lead to new directions for limiting breast cancer metastasis.
Receptor-receptor interactions of complement receptor type 3 in neutrophil membranes
Authors: Petty Howard R , Todd Robert R 
Published: January 2018

Abstract
The leukocyte integrin CR3 (GDllb/CD18) is known to participate in a variety of cell functions. Recent studies have indicated that CR3 may communicate with other plasma membrane receptors to carry out several cell functions. In this review we discuss these potential receptor-receptor interactions of CR3 and present a unifying model of GR3’s diverse functions.
Detection of intracellular interferon-γ by light microscopy using an immunoperoxidase technique: correlation with the corresponding mRNA and protein product
Authors: Dolhain Radboud J E M , Andersson Ulf , ter Haar Natalja T , Brinkman Brigitta M N , Verweij Cornells L , Daha Mohamed R , Breedveld Ferdinand C , Miltenburg Andre M M 
Published: January 2018

Abstract
Identifying individual cytokine-producing cells may help to acquire insight into immunological processes. This study was designed to adapt a technique for the detection of individual cytokine-producing cells from an immunofluorescence to an immunoperoxidase staining procedure. The production of interferon-γ (IFN-γ) by anti-CD3-activated cloned human T cells was used as a model system. After the conditions for the staining procedure were optimized, the immunoperoxidase technique was slightly more sensitive than the immunofluorescence technique. The intracellular staining for IFN-γ was preceded or paralleled by IFN-γ mRNA production and followed by accumulation of IFN-γ in the supernatant. It is concluded that intracellular IFN-γ can easily be detected using an immunoperoxidase procedure. This procedure is highly sensitive and allows quantification of the production of multiple cytokines by counting the percentage of positively staining cells.
Transient exposure of human eosinophils to the protein kinase C inhibitors CGP39-360, CGP41-251, and CGP44-800 leads to priming of the respiratory burst induced by opsonized particles
Authors: van der Bruggen Tjomme , Kbk Paul T M , Blom Michela , Verhoeven Arthur J , Raaijmakars Jan A M , Lammers Jan-Willem J , Koenderman Leo 
Published: January 2018

Abstract
We report that a transient incubation of human eosinophils with the protein kinase C (PKG) inhibitor CGP39-360 (staurosporine) or the more PKC-specific inhibitors CGP41-251 and CGP44-800 prior to activation of the respiratory burst with opsonized particles results in priming of this response. This priming effect was concentration dependent and occurred in the range in which the phorbol myristate acetate-induced respiratory burst was inhibited. CGP39-360 priming was minimally affected in Ca2+-depleted cells, indicating that an increase in [Ca2+]i is not important. Also, the binding of serum-treated zymosan (STZ) particles was strongly enhanced by the inhibitors. On the other hand, the release of plateletactivating factor (PAF) induced by opsonized particles was enhanced only by CGP39-360 and not by CGP41-251 and CGP44-800. Therefore, priming of the respiratory burst is not due to an aspecific enhancing effect of the inhibitors. These data indicate that different signal transduction routes are involved in priming of the STZ-induced respiratory burst and PAF release in human eosinophils.
Increased expression of a novel leukocytic factor in patients with hemolytic anemia
Authors: Larochelie André , Marceau Danièle , de Médicis Eveline 
Published: January 2018

Abstract
Misprimed polymerase chain reaction (PGR) products were generated from the crude leukocytic DNA extract of four of five patients with hereditary hemolytic anemia, during the course of exon 6 pyruvate kinase L gene amplification. These by-products, which originated from abundant mRNA templates, were not observed in seven healthy individuals. Two markers were cloned (GenBank accession numbers M64700 and M64701). We focused further studies on one of the human markers associated with hereditary hemolytic anemia, human DNA marker B (HUMDNAMB). HUMDNAMB is a 451-bp open reading frame that has never been described previously. The nucleic acid sequence region 303–416 is 63% homologous to a coding region of the bovine interferon α-A gene. Matrix analysis of the amino acid sequences reveals a structural similarity between the two proteins. The HUMDNAMB protein is expected to be larger than interferons, based on the size of its 2-kb messenger RNA detected by Northern blot in human leukocytes, fetal liver, and fetal intestine. J. Leukoc. Biol. 55: 1–6; 1994.
Ligation of N-acetylgalactosamine–containing structures on rat bone marrow cells enhances myeloid differentiation and murine granulocyte-macrophage colony-stimulating factor-induced proliferation
Authors: Krugluger Walter , Köller Marcus , Allmaier Martina , Boltz-Nitulescu George , Förster Othmar 
Published: January 2018

Abstract
Previously we have reported the differentiation-dependent expression of a soybean agglutinin (SBA)-binding structure on rat bone marrow cells (BMCs) during their differentiation into macrophages (møs). In the present study we tried to analyze the functional role of the SBA-binding structure in BMC proliferation and differentiation. Addition of SBA to BMC cultures driven into mø differentiation by recombinant murine granulocyte-macrophage colony-stimulating factor (rmGM-CSF), resulted in a two- to threefold increased proliferation rate compared with rmGM-CSF alone. However, the number of colonies in methyl cellulose was not increased by SBA. The effect of SBA was dose dependent (from 4 to 83 pM SBA), with a maximum effect at 83 pM. Experiments to detect a possible synergistic effect of additional cytokines produced by BMC after SBA treatment were inconclusive. The enhancing effect of SBA was also seen when high-density cells, which did not proliferate in response to rmGM-CSF (mainly granulocytes), were removed. Therefore, SBA may increase the CSF reactivity of re-sponsive mø progenitor cells directly by binding to N-acetylgalactosamine residues on their surface. J. Leukoc. Biol. 55: 127–132; 1994.