bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glucocorticoids protect against suppression of T cell responses in a murine model of acute ethanol exposure and thermal injury by regulating IL-6
Authors: Faunce Douglas E , Gregory Meredith S , Kovacs Elizabeth J 
Published: January 2018

Abstract
Previous reports by this laboratory demonstrated that acute alcohol exposure combined with a 15% body surface area dorsal scald injury results in significant reductions in delayed-type hypersensitivity (DTH) and splenocyte proliferative responses compared to either insult alone. Previous studies by this lab have also shown that these defects are mediated, in part, by increased production of interleukin-6 (IL-6). Because both alcohol exposure and thermal injury are known to modulate glucocorticoid (CORT) levels, and CORT regulates IL-6 gene expression, the relationship between circulating CORT and IL-6 production in burn + ethanol mice was examined . At 24 and 48 h post-burn, a positive correlation existed between circulating CORT levels and measurements of cellular immune function. Administration of exogenous CORT to burn + ethanol-treated mice resulted in significant restoration (to 60% of control) of DTH and splenocyte proliferative responses. This restoration was concomitant with a down-regulation of circulating and macrophage-derived IL-6. The specificity of CORT in modulating these responses was tested by assessing cellular immune function and IL-6 levels after glucocorticoid receptor blockade with RU486. Taken together, these data strongly suggest that under normal circumstances CORT protects burned mice from severe immune dysfunction, a protection that is not afforded to burn + ethanol-treated mice. Furthermore, the immune dysfunction observed in burn + ethanol mice may be due to a lack of glucocorticoid attenuation of IL-6. J. Leukoc. Biol. 64: 724–732; 1998.
Role of ICAM-1 and ICAM-2 and alternate CD11/CD18 ligands in neutrophil transendothelial migration
Authors: Issekutz Andrew C , Rowter Derek , Springe Timothy A 
Published: January 2018

Abstract
We evaluated the relative contribution of ICAM-1 and ICAM-2, known ligands on endothelium for LFA-1 and Mac-1, in spontaneous neutrophil (PMN) transendothelial migration (TEM) across IL-1-activated HUVEC monolayers or TEM induced by C5a or IL-8 across unstimulated HUVEC grown on polycarbonate filters. Adhesion blocking mAb to ICAM-1 [R6.5 F(ab)2] or ICAM-2 [CBR IC2/2 F(ab)2] tended to inhibit TEM under each condition but, in general, inhibition was significant only with both ICAM-1 and ICAM-2 blockade. mAb to LFA-1 partially inhibited migration to C5a or IL-8 across unstimulated HUVEC and inhibition was not altered by additional treatment of HUVEC with mAbs to ICAM-1 and -2. In contrast, with IL-1 HUVEC, mAb to ICAM-1 significantly inhibited this LFA-1-independent TEM. mAb to Mac-1 alone partially inhibited TEM and, when combined with mAb to LFA-1, migration was almost completely blocked with all TEM conditions tested. The contribution of alternate ligands for Mac-1 in mediating Mac-1-dependent but ICAM-1/-2-independent C5a-induced TEM was examined using anti-LFA-1-treated PMN and anti-ICAM-treated resting HUVEC. Addition of RGD peptides, fibronectin, fibrinogen, heparins, collagens alone or in combination, even to heparinase-treated HUVEC, did not inhibit this Mac-1-mediated PMN TEM. The results indicate that: (1) LFA-1 mediates PMN TEM primarily by interaction with ICAM-1 and ICAM-2; (2) ICAM-2 may function in concert with ICAM-1 in this role, especially on unstimulated endothelium, and (3) Mac-1 on PMN also plays a major role in TEM and can utilize yet to be identified ligands distinct from ICAM-1 or -2, especially on unstimulated endothelium. J. Leukoc. Biol. 65: 117–126; 1999.
Macrophage phagocytosis of wound neutrophils
Authors: Meszaros Adriana J , Reichner Jonathan S , Albina Jorge E 
Published: January 2018

Abstract
Resolution of acute inflammation is thought to require the recognition and phagocytosis of apoptotic neutrophils (PMN) through receptor-ligand interactions with macrophages (Mϕ). This hypothesis was tested in rat wounds by quantifying apoptosis in freshly harvested and aged-in-culture PMN taken from wounds 1–3 days after injury and by using these wound PMN as phagocytic targets for wound, immune-activated peritoneal, and resident peritoneal Mϕ. Less than 6% of freshly harvested PMN exhibited characteristics of apoptosis. On aging in culture, day 1 PMN did not undergo apoptosis, whereas 41 ± 1 and 29 ± 1% of day 2 and 3 PMN, respectively, developed apoptosis, which corresponded to increased ingestion by Mϕ. All three Mϕ populations engaged different receptor-ligand pairs for the recognition and phagocytosis of PMN. Results indicate the resistance of early wound PMN to age-induced apoptosis, demonstrate wound-Mϕ phagocytosis of wound PMN, and identify distinct receptor utilization by wound and other Mϕ to ingest wound PMN. J. Leukoc. Biol. 65:35–42; 1999.
Soluble vascular cell adhesion molecule (VCAM)-Fc fusion protein induces leukotriene C4 secretion in platelet-activating factor-stimulated eosinophils
Authors: Tsuruta Ryosuke , Cobb Ronald R , Mastrangelo Marian , Lazarides Elias , Cardarelli Pina M 
Published: January 2018

Abstract
Eosinophil adhesion to vascular cell adhesion molecule-1 (VCAM-1) is important for cellular recruitment into allergic inflammatory sites. To determine whether eosinophil adhesion to VCAM-1 affects cell function, leukotriene C4 (LTC4) was measured. Human eosinophils were incubated with platelet-activating factor (PAF) in the presence or absence of soluble VCAM-Fc fusion protein (sVCAM-Fc) or immobilized VCAM-Fc. sVCAM-Fc induced a concentration-dependent increase in LTC4 secretion, which was dependent on the presence of PAF and not blocked by cyclic peptides shown to inhibit α4β1-dependent adhesion. Likewise, soluble ICAM-Fc induced a concentration- dependent LTC4 secretion. LTC4 secretion was induced by the calcium ionophore, A23187, and the combination of sVCAM-Fc and A23187 had synergistic properties. It is interesting to note that Mn2+ or anti-β1 monoclonal antibody, TS2/16, inhibited LTC4 secretion induced by sVCAM-Fc and PAF. Eosinophil adhesion to VCAM-Fc or interleukin-1β-stimulated endothelial cells did not induce LTC4 secretion. These data suggest that sVCAM-Fc-induced LTC4 secretion depends on distinct signals from those of eosinophil adhesion. J. Leukoc. Biol. 65: 71–79; 1999.
Comparison of suppressive effects of a new anti-inflammatory compound, FR167653, on production of PGE2 and inflammatory cytokines, human monocytes, and alveolar macrophages in response to endotoxin
Authors: Kawano Tetsuya , Ogushi Fumitaka , Tani Kenji , Endo Takeshi , Ohmoto Yasukazu , Hayashi Yoko , Sone Saburo 
Published: January 2018

Abstract
FR167653 {1-[7-(4-fluorophenyl)-1, 2, 3, 4-tetrahydro-8 (4-pyridyl) pyrazoro [5-1-c] [1, 2, 4] triazin-2-yl]-2-phenylethanedion sulfate monohydrate} was developed to inhibit proinflammatory cytokine production. However, the effects of FR167653 on prostanoid production are unclear. We investigated the effect of FR167653 on proinflammatory cytokine and prostaglandin (PG) production by lipopolysaccharide (LPS)-stimulated human peripheral blood monocytes and alveolar macrophages (AM) from the same individuals, and compared the effects in monocytes and AM. FR167653 inhibited interleukin-1β and tumor necrosis factor a production. The effect on PGE2 production was assessed by four parameters. FR167653 inhibited PGE2 synthesis and LPS induction of cyclooxygenase activity. Western and Northern blot analyses revealed that LPS induction of cyclooxygenase-2 expression was attenuated by this compound. The suppression in monocytes was greater than that in AM. We concluded that the reduction of LPS-induced PGE2 synthesis by FR167653 was due to inhibition of cyclooxygenase-2 production. These results show that FR167653 may be therapeutically useful for inhibiting production of both inflammatory cytokines and PG production in inflammatory diseases. J. Leukoc. Biol. 65: 80–86; 1999.
Trp-Lys-Tyr-Met-Val-D-Met stimulates superoxide generation and killing of Staphylococcus aureus via phospholipase D activation in human monocytes
Authors: Bae Yoe-Sik , Ju Seong-A , Kim Ji Yung , Seo Jeong Kon , Baek Suk Hwan , Kwak Jong-Young , Kim Byung Sam , Suh Pann-Ghill , Ryu Sung Ho 
Published: January 2018

Abstract
Among the phagocytic leukocytes, monocytes have the important role of clearing out parasitic microorganisms. They accomplish this through production of toxic metabolites of oxygen. Trp-Lys-Tyr-Met-Val-D-Met (WKYMVm), a peptide that stimulates phosphoinositide (PI) hydrolysis in human leukocytes, including monocytes, binds to a unique cell surface receptor and stimulates superoxide generation, killing of Staphylococcus aureus, and activation of phospholipase D (PLD) in human monocytes. Preincubation of the cells with a PI-specific phospholipase C (PLC) inhibitor (U-73122), protein kinase C inhibitor (GF109203X), or intracellular Ca2+ chelator (BAPTA/AM) before the peptide stimulus totally inhibits the peptide-induced PLD activation and superoxide generation. On the other hand, tyrosine kinase inhibitor genistein only partially inhibits the peptide-induced processes. The peptide-induced bacteria killing activity shares regulatory mechanisms for PLD activation with the superoxide generation, which is inhibited in the presence of 1-butanol. We suggest that the peptide stimulates PLD downstream of PLC activation and PLD activation in turn is essential for the peptide-induced immunological functions such as the superoxide generation and killing of bacteria by human monocytes. J. Leukoc. Biol. 65:241–248; 1999.
LPS down-regulates the expression of chemokine receptor CCR2 in mice and abolishes macrophage infiltration in acute inflammation
Authors: Zhou Yuhong , Yang Yi , Warr Glenn , Bravo Rodrigo 
Published: January 2018

Abstract
Interactions between chemokines and their specific receptors are important for leukocyte trafficking. The CC-chemokine monocyte chemoattractant protein-1 (MCP-1) and its specific receptor CCR2 are essential in monocytic infiltration and have been associated with several inflammatory diseases. It has been reported that several endotoxin and proinflammatory cytokines inhibit CCR2 expression in vitro in human monocytes. We report here that lipopolysaccharides (LPS) down-regulated CCR2 expression both in vitro and in vivo. Injection of LPS into mice dramatically reduced the expression of CCR2 on the surface of peripheral blood cells and completely blocked macrophage infiltration into the peritoneal cavity in response to thioglycollate elicitation. In addition, treatment of mice with LPS reduced their efficiency to clear Listeria monocytogenes infection. These results suggest that down-regulation of CCR2 and blockage of monocyte infiltration may contribute to the inhibition of macrophage function in vivo by a low dose of LPS. J. Leukoc. Biol. 65: 265–269; 1999.
Regulation of arachidonic acid release and cytosolic Phospholipase A2 activation
Authors: Gijón Miguel A , Leslie Christina C 
Published: January 2018

Abstract
The 85-kDa cytosolic PLA2 (CPLA2) mediates agonist-induced arachidonic acid release in many cell models, including mouse peritoneal macrophages. cPLA2 is regulated by an increase in intracellular calcium, which binds to an amino- terminal C2 domain and induces its translocation to the nuclear envelope and endoplasmic reticulum. Phosphorylation of cPLA2 on S505 by mitogen-activated protein kinases (MAPK) also contributes to activation. In macrophages, zymosan induces a transient increase in intracellular calcium and activation of MAPK, which together fully activate cPLA2 and synergistically promote arachidonic acid release. There are alternative pathways for regulating cPLA2 in macrophages because PMA and okadaic acid induce arachidonic acid release without increasing calcium. The baculovirus expression system is a useful model to study cPLA2 activation. Sf9 cells expressing cPLA2 release arachidonic acid to either A23187 or okadaic acid. cPLA2 is phosphorylated on multiple sites in Sf9 cells, and phosphorylation of S727 is preferentially induced by okadaic acid. However, the phosphorylation sites are non-essential and only S505 phosphorylation partially contributes to cPLA2 activation in this model. Although okadaic acid does not increase intracellular calcium in Sf9 cells, calcium binding by the C2 domain is necessary for arachidonic acid release. A23187 and okadaic acid activate cPLA2 by different mechanisms, yet both induce translocation to the nuclear envelope in Sf9 cells. The results demonstrate that alternative regulatory pathways can lead to cPLA2 activation and arachidonic acid release. J. Leukoc. Biol. 65: 330–336; 1999.
Kinases involved in MSP/RON signaling
Authors: Danilkovitch Alla , Leonard Edward J 
Published: January 2018

Abstract
Macrophage stimulating protein (MSP) belongs to the plasminogen-related kringle domain family. In addition to stimulation of macrophages, MSP acts on other cell types including epithelial and hematopoietic cells. The MSP receptor is a transmembrane tyrosine kinase called RON in humans and STK in mice. MSP/receptor interaction induces activation of signal transduction pathways that mediate MSP biological activities. Cytoplasmic kinases are intracellular messengers occupying an important role in signal transduction. We have identified kinases that participate in RON signaling. In addition to previously identified involvement of phosphatidylinositol 3-kinase (PI3-K), JNK, and MAPK, we found that FAK, c-Src, and AKT are rapidly and transiently activated by MSP. FAK, MAPK, and c-Src are involved in MSP-induced cell proliferation. MAPK and c-Src are components of one signal transduction cascade, and MAPK is downstream of c-Src. FAK also regulates MSPinduced cell growth, but via a path different from c-Src/MAPK. AKT kinase is a component of a separate branch of the RON/PI3-K pathway that mediates the MSP anti-apoptotic effect on epithelial cells. PI3-K regulates MSP-induced adhesion and motility but via downstream components different from AKT. Thus, occupancy of the RON receptor by MSP activates distinct signal transduction pathways that mediate several cellular responses. J. Leukoc. Biol. 65: 345–348; 1999.
Antibodies to CD18 influence neutrophil migration through extracellular matrix
Authors: Saltzman W Mark , Livingston Treena L , Parkhurst Maria R 
Published: January 2018

Abstract
Mac-1 (CD11b/CD18) is known to be involved in neutrophil (PMN) adhesion to endothelial cells and extracellular matrix. Although antibodies to CD18 are being tested for therapy in humans, their role in PMN migration through the extracellular matrix is unknown. We used direct visualization to quantify PMN motility through reconstituted, three-dimensional gels of collagen type I. Gels were prepared with different concentrations of collagen (ranging from 0.1 to 1.0 mg/mL) and PMN migration was examined in the presence and absence of antibodies to CD18 (anti-CD18), with and without stimulation by N-formyl peptides. In low-concentration gels (&lt;0.6 mg/mL), anti-CD18 had a significant influence on PMN migration, increasing motility in unstimulated PMN by 90% at 0.3 mg/mL collagen, and decreasing motility in N-formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated PMN by 70% at 0.4 mg/mL collagen. But anti-CD18 had no effect on the rate of cell migration through high-concentration collagen gels (&gt;0.6 mg/mL). PMN migration through collagen gels is CD18-dependent but only under conditions of high hydration, suggesting that CD18-mediated effects (e.g., adhesion to gel fibers) are only important when the fiber density is relatively low. Anti-CD18 inhibited, but did not eliminate, the adhesion of fMLP-stimulated PMN to the surface of collagen gels, suggesting that cells use multiple mechanisms for gaining traction within the gel. Because of the multiple modes of interaction between motile cells and the deformable fiber matrix, blockade of one component, such as CD18, can enhance the rate of cell migration under one set of conditions, and inhibit under another. J. Leukoc. Biol. 65: 356–363; 1999.
Neutrophils isolated from leprosy patients release TNF-α and exhibit accelerated apoptosis in vitro
Authors: Oliveira R B , Moraes M O , Oliveira E B , Sarno E N , Nery J A C , Sampaio E P 
Published: January 2018

Abstract
This study demonstrated that polymorphonuclear neutrophils (PMN) participate in the acute inflammatory response in leprosy as effector cells. Lepromatous patients present intense infiltrate of neutrophils in reactional (ENL) lesions. Circulating PMN of nonreactional patients, healthy donors, and reactional patients were purified and analyzed in vitro. The study confirmed the short lifespan of these cells in culture with progressive changes characteristic of apoptosis. Apoptosis was greatly accelerated in ENL patients as shown by cellular morphology, later confirmed by qualitative and quantitative analysis of fragmented DNA. It was observed that neutrophils stimulated with lipopolysaccharide, Mycobacterium leprae, and lipoarabinomannan secrete interleukin-8 and tumor necrosis factor α (TNF-α). Thalidomide, a drug known to inhibit TNF-α synthesis on monocytes, also exerted an inibitory effect on TNF-α secretion in neutrophils. These data suggest that PMN can participate in the regulation of the immune response in leprosy and can contribute to the amplification of TNF-α production at the site of ENL lesion. J. Leukoc. Biol. 65: 364–371; 1999.
Co-expression of several human syntaxin genes in neutrophils and differentiating HL-60 cells: variant isoforms and detection of syntaxin 1
Authors: Martín-Martín Belén , Nabokina Svetlana M , Lazo Pedro A , Mollinedo Faustino 
Published: January 2018

Abstract
Syntaxins are major components of vesicle trafficking and their pattern of expression depends on the cell type. Using reverse transcriptase-polymerase chain reaction (RT-PCR), cloning, and sequencing techniques, we have found that human neutrophils and neutrophil-differentiated HL-60 cells co-express syntaxins 1A, 3, 4, 5, 6, 7, 9, 11, and 16. These genes are also expressed in human peripheral blood lymphocytes and SH-SY5Y neuroblastoma cells, which, unlike neutrophils, also expressed syntaxin 10. We have identified two isoforms of syntaxin 3. Syntaxin 3A, similar to the previously reported syntaxin 3, and the novel isoform syntaxin 3B, which is identical to syntaxin 3A but lacks 37 amino acid residues at the carboxy-terminal region. Syntaxin 1 was mainly located to neutrophil granule membranes by confocal microscopy and by immunoblotting of subcellular fractions. These data indicate that syntaxin 1 cannot be considered specific to neural tissues. The level of expression of syntaxins 3, 4, 6, and 11 was increased during neutrophil differentiation ofHL-60 cells, whereas that of syntaxins 1A, 5, 9, and 16 was unchanged. Syntaxin 7 was not expressed in undifferentiated HL-60 cells, but its expression was induced on neutrophil differentiation. The expression of several syntaxin genes in human neutrophils could be related to the high secretory capacity of these cells as well as to the presence of different cytoplasmic granules with distinct exocytic capabilities. J. Leukoc. Biol. 65: 397–406; 1999.
Viral variant nucleotide sequences help expose leukocytic positioning in the JC virus pathway to the CNS
Authors: Jensen Peter N , Major Eugene O 
Published: January 2018

Abstract
The human polyomavirus JCV lytically infects oligodendrocytes of immunosuppressed individuals leading to the fatal demyelinating disease termed progressive multifocal leukoencephalopathy (PML). Dementia, hemiparesis, and hemianopsia are the predominant presenting signs of PML. Asymptomatic JCV infection is common worldwide with approximately 80% of adults testing positive for JCV antibodies. In addition to the brain, JCV has been shown to infect tonsil, lymphoid, bone marrow, and kidney tissues. Viral variants, classified according to the nucleotide sequences of their regulatory regions, are being mapped in human tissues and cell types to help trace the pathway of JCV from a site of initial infection to target oligodendrocytes. In most literature, a dichotomy of the JCV regulatory region structure exists by tissue. B lymphocytes, however, have demonstrated the capacity to harbor JCV of diverse regulatory regions, which helps position their interaction with virus amid every stage of infection and implicates a lymphocytic role in latency. J. Leukoc. Biol. 65: 428–438; 1999.
Interferon response heterogeneity: activation of a pro-inflammatory response by interferon α and β. A possible basis for diverse responses to interferon β in MS
Authors: Jansen Marilyn , Reinhard John F 
Published: January 2018

Abstract
Interferon γ (IFN-γ) stimulates the (pro-inflammatory) type II interferon receptor and is known to exacerbate multiple sclerosis (MS). In contrast, IFN-α and IFN-β are ligands for the (anti-inflammatory) type I interferon receptor and are beneficial in some (but not all) patients with MS. Should IFN-β elicit a type-II-like pro-inflammatory response, the beneficial effects might be attenuated. These studies were undertaken to test this possibility with the use of quinolinic acid (QUIN) formation as a measure of type II receptor activation. In normal human macrophage cultures, IFN-γ was the most potent stimulus for QUIN formation. Generally, IFN-β and IFN-α were less potent. However, an unexpected inter-patient variability was observed. In some subjects, IFN-α was more potent than IFN-β. In other subjects, IFN-β was more potent than IFN-α. The present data demonstrate an inter-subject variability for QUIN production following exposure to the interferons. MS patients who demonstrate a pro-inflammatory response to IFN-β (e.g., increased QUIN) may be less likely to benefit from this therapy. J. Leukoc. Biol. 65: 439–443; 1999.
Do alcohol and cocaine abuse alter the course of HIV-associated dementia complex?
Authors: Tyor William R , Middaugh Lawrence D 
Published: January 2018

Abstract
Although psychoactive drugs are commonly used by AIDS patients, it is unclear whether commonly abused drugs, such as cocaine and ethanol, affect the course of HIV-associated dementia (HADC). Epidemiological studies have resulted in conflicting conclusions as to what role, if any, abused drugs play in HADC. In this review we discuss the clinical and pathological evidence that cocaine and ethanol might exacerbate the detrimental effects of HIV infection on the brain. We also review studies of cocaine and ethanol effects on various components of the immune system both in the presence and absence of retroviral infection. Data from these studies indicate that cocaine and ethanol have profound effects on the immune system that, in many respects, are enhanced by retroviral infection. We conclude that abused drugs likely affect the course of HADC but that proof awaits an examination of their interactive effects in an appropriate in vivo system of retroviral encephalitis. J. Leukoc. Biol. 65: 475–481; 1999.