bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of CD8+ and WC-1+ γ/δ T cells in resistance to Mycobacterium bovis infection in the SCID-bo mouse
Authors: Smith Ruth A , Kreeger John M , Alvarez Antonio J , Goin Jessica C , Davis William C , Whipple Diana L , Estes D Mark 
Published: January 2018

Abstract
The role of various effector T cell populations in the bovine immune response to Mycobacterium bovis infection is poorly understood. This is largely due to the difficulties associated with performing in vivo challenge studies in the natural host species. In this report, we utilized a fetal bovine-severe combined immunodeficient (SCID-bo) xenochimeric mouse model to study the protective role of two putative effector cell types, CD8+ T cells and a subpopulation of γ/δ T cells that express WC-1, a member of the cysteine-rich scavenger receptor superfamily (CRSR). We demonstrate that CD8+ T cells play a key role in protection and contribute substantially to bovine IFN-γ mRNA levels at 30 days post-infection. The role of WC-1 bearing cells to protection was less definitive but our results suggest that this population may play a pivotal role early in infection. Granuloma architecture was altered in anti-WC-1 (ILA29) but not anti-CD8 (ILA51) -treated animals, suggesting that this population may be involved in recruitment of various cell types to sites of infection. J. Leukoc. Biol. 65: 28–34; 1999.
P-selectin mediates neutrophil adhesion to endothelial cell borders
Authors: Burns Alan R , Bowden Robert A , Abe Yasunori , Walker David C , Simon Scott I , Entman Mark L , Smith C Wayne 
Published: January 2018

Abstract
During an acute inflammatory response, endothelial P-selectin (CD62P) can mediate the initial capture of neutrophils from the free flowing bloodstream. P-selectin is stored in secretory granules (Weibel-Palade bodies) and is rapidly expressed on the endothelial surface after stimulation with histamine or thrombin. Because neutrophil transmigration occurs preferentially at endothelial borders, we wished to determine whether P-selectin-dependent neutrophil capture (adhesion) occurs at endothelial cell borders. Under static or hydrodynamic flow (2 dyn/cm2) conditions, histamine (10-4 M) or thrombin (0.2 U/mL) treatment induced preferential (≥ 75%) neutrophil adhesion to the cell borders of endothelial monolayers. Blocking antibody studies established that neutrophil adhesion was completely P-selectin dependent. P-selectin surface expression increased significantly after histamine treatment and P-selectin immunostaining was concentrated along endothelial borders. We conclude that preferential P-selectin expression along endothelial borders may be an important mechanism for targeting neutrophil migration at endothelial borders. J. Leukoc. Biol. 65: 299–306; 1999.
The cellular immunology of multiple sclerosis
Authors: Al-Omaishi Jinan , Bashir Rifaat , Gendelman Howard E 
Published: January 2018

Abstract
Multiple sclerosis (MS) is a neurological disease that affects the central nervous system (brain and spinal cord) resulting in debilitating motor and sensory dysfunction. Its mean age of onset is 30 years and, with the exception of trauma, MS remains the most frequent cause of neurological disabilities for young adults. The disease is highly variable in its onset and progression. It may not be easily diagnosed, at least in its earliest stages. Significant disability is a hallmark of MS. Indeed, up to 50% of patients require walking aids and 10% are wheelchair-bound at 15 years after an initial diagnosis. Clinical features include deficits in sensory (parasthesias and numbness), motor (difficulties with fine movements and gait), balance, bladder, and sexual functions. Although the etiology for MS is not yet known, it is thought to be related to microbial, genetic, and/or environmental factors. Pathologically, MS is characterized by inflammation. An influx of mononuclear cells occurs through a disrupted blood–brain barrier into an immune-privileged central nervous system. The secretion of a variety of inflammatory cytokines and chemokines from glial cells leads to loss of myelin, disruption of oligodendrocyte integrity, and axonal loss. These events, in large measure, affect progressive neural atrophy. How brain inflammatory activities affect transendothelial migration of leukocytes into the brain and alter the process of myelination are the focal points for MS research activities. J. Leukoc. Biol. 65: 444-452; 1999.
Macrophage invasion does not contribute to muscle membrane injury during inflammation
Authors: Tidball James G , Berchenko Eugene , Frenette Jérôme 
Published: January 2018

Abstract
Previous observations have shown that neutrophil invasion precedes macrophage invasion during muscle inflammation and that peak muscle injury is observed at the peak of ED1+ macrophage invasion. We tested the hypothesis that neutrophil invasion causes subsequent invasion by ED1+ macrophages and that ED1+ macrophages then contribute significantly to muscle membrane injury during modified muscle use. Rat hindlimbs were unloaded for 10 days followed by reloading by normal ambulation to induce inflammation. Membrane injury was measured by assaying Evans blue-bound serum protein influx through membrane lesions. Muscle neutrophil populations increased significantly during the first 2 h of reloading but ED1+ macrophages did not increase until 24 h. Neutrophil invasion was uncoupled from subsequent macrophage invasion by reloading rat hindlimbs for 2hto cause neutrophil invasion, followed by resuspension for hours 2–24. This produced similar increases in neutrophil concentration as measured in muscles continuously reloaded for 24 h without causing an increase in macrophages. However, resuspension did not reduce the extent of muscle damage compared with that occurring in muscles that were reloaded continuously for 24 h. Thus, muscle invasion by neutrophils is not sufficient to cause invasion by ED1+ macrophages. In addition, muscle membrane injury that occurs during reloading is independent of invasion by ED1+ macrophages. J. Leukoc. Biol. 65: 492–498; 1999.
Differential production of MCP-1 and cytokine-induced neutrophil chemoattractant in the ischemic brain after transient focal ischemia in rats
Authors: Yamagami Shinsuke , Tamura Mizuho , Hayashi Minoru , Endo Noriaki , Tanabe Hirofumi , Katsuura Yasuhiro , Komoriya Keiji 
Published: January 2018

Abstract
Chemokines have been shown to play an important role in leukocyte infiltration into ischemic lesions. Recently, the increased expression of monocyte chemoattractant protein-1 (MCP-1) and cytokine-induced neutrophil chemoattractant (CINC) was observed in experimental stroke models where infiltrated leukocytes were supposed to induce tissue injury, however, the protein level and time course of these chemokines have not been fully elucidated. Therefore, we analyzed the time-dependent production of MCP-1 and CINC in the rat brain after transient middle cerebral artery occlusion (MCAO) by means of specific enzyme-linked immunosorbent assay systems. The MCP-1 levels in the ipsilateral hemispheres increased from 6 h, peaked at 2 days, and thereafter gradually decreased. The peak MCP-1 concentration was 89.2 ± 28.2 ng/g tissue wet weight (mean ± sem, n = 5, 49.3-fold greater than the contralateral value at the same time, P &lt; 0.05), which is supposed to be high enough to exert its biological effects. In contrast, the maximum CINC concentration that corresponded to 2.9 ± 0.7 ng/g tissue wet weight (mean ± sem, n = 5, 55.0-fold greater than the contralateral value at the same time, P &lt; 0.05), was observed at 6 h. In addition, we confirmed the temporal profile of leukocyte subtypes that infiltrated into the ischemic brain, thus, neutrophil infiltration occurred at early stages (1–3 days), followed by massive infiltration of macrophages at later stages (2–7 days). These studies suggest that MCP-1 in cerebral ischemia actually plays a significant role in the migration of macrophages into the lesion and that the differential temporal production of these chemokines contributes to the regulation of infiltrated leukocyte subtypes. J. Leukoc. Biol. 65: 744–749; 1999.
Blockade of nitric oxide formation down-regulates cyclooxygenase-2 and decreases PGE2 biosynthesis in macrophages
Authors: Perkins Douglas J , Kniss Douglas A 
Published: January 2018

Abstract
Elevated levels of nitric oxide (NO) produced by expression of inducible nitric oxide synthase (iNOS/NOS type 2) and high levels of prostaglandins (PGs) generated by expression of inducible cyclooxygenase (COX-2/PGH2 synthase-2) are important mediators of immune and inflammatory responses. Previous studies have shown that endogenous levels of NO˙ can influence the formation of PGs. We examined the mechanism by which NO˙ regulates PG biosynthesis in macrophages. Treatment of a murine macrophage cell line (ANA-1) with lipopolysaccharide (LPS, 10 ng/mL) and interferon-γ (IFN-γ, 10 U/mL) for 20 h elicited high levels of nitrite (NO2−) and prostaglandin E2 (PGE2) that were inhibited in a dose-dependent fashion by the NOS inhibitor, aminoguanidine (AG), with IC50 values of 15.06 and 0.38 μM for NO2− and PGE2, respectively. Stimulation of cultures with LPS and IFN-γ for 20 h induced de novo iNOS protein expression that was not altered by the addition of AG (0.1, 10, or 1000 γM). In contrast, treatment of cultures with LPS and IFN-γ for 20 h promoted COX-2 mRNA and protein expression that were decreased in a dose-dependent fashion by AG (P &lt; 0.05 with 10 and 1000 μM). LPS and IFN-γ-induced COX-2 protein expression was not decreased in cultures treated with AG for 2 h, illustrating that AG does not inhibit the formation of COX-2 protein. Analysis of partially purified enzyme extracts demonstrated that AG did not directly inhibit the enzymatic activity of COX. Additional experiments revealed that NO^ donors (S-nitroso-N-aceytl-d-l-pencillamine, SNAP, at 0.1, 10, and 1000 μM) did not induce de novo COX-2 protein expression or potentiate COX-2 expression in cells treated with LPS and/or IFN-γ. Our results suggest that, while endogenous NO˙ is not required for de novo COX-2 mRNA and protein expression, NO˙ is necessary for maintaining prolonged COX-2 gene expression. J. Leukoc. Biol. 65: 792–799; 1999.
Inhibition of microglial cell RANTES production by IL-10 and TGF-β
Authors: Hu Shuxian , Chao Chun C , Ehrlich Laura C , Sheng Wen S , Sutton Richard L , Rockswold Gaylan L , Peterson Phillip K 
Published: January 2018

Abstract
Using human fetal microglial cell cultures, we found that the gram-negative bacterial cell wall component lipopolysaccharide (LPS) stimulated RANTES (regulated upon activation of normal T cell expressed and secreted) production through the protein kinase C signaling pathway and that activation of transcription nuclear factor (NF)-κB was required for this effect. Similarly, the proinflammatory cytokines interleukin (IL)-1β and tumor necrosis factor-α dose-dependently stimulated microglial cell RANTES production via NF-κB activation. Anti-inflammatory cytokines, IL-10, and transforming growth factor (TGF)-β sequentially inhibited LPS- and cytokine-induced microglial cell NF-κB activation, RANTES mRNA expression, and protein release. Proinflammatory cytokines but not LPS also stimulated RANTES production by human astrocytes. These findings demonstrate that human microglia synthesize RANTES in response to proinflammatory stimuli, and that the anti-inflammatory cytokines IL-10 and TGF-β down-regulate the production of this β-chemokine. These results may have important therapeutic implications for inflammatory diseases of the brain. J. Leukoc. Biol. 65: 815–821; 1999.
ICAM-3 (CD50) cross-linking augments signaling in CD3-activated peripheral human T lymphocytes
Authors: Berney Seth Mark , Schaan Tonya , Alexander J Steven , Peterman Gary , Hoffman Patricia A , Wolf Robert E , van der Heyde Henri , Atkinson T Prescott 
Published: January 2018

Abstract
ICAM-3 is a pan-hematopoietic, constitutive adhesion molecule. ICAM-3 binds to LFA-1 on antigen-presenting cells (APC) stabilizing the T cell-APC interaction, facilitating signaling through the CD3/TCR complex. However, recent evidence using cultured and transformed T cells suggests ICAM-3 may also function in signaling. Because ICAM-3 is constitutively expressed on resting T cells, we postulated that signaling through ICAM-3 in resting T cells represents an important costimulatory mechanism in these cells. In purified resting human T cells, cross-linking both ICAM-3 and CD3 with plate-bound antibodies resulted in a marked increase in cell size (consistent with blastogenesis), synergistically increased surface expression of CD25 and CD69, and increased T cell metabolism. Similarly, concomitant ICAM-3 and CD3 stimulation significantly (P &lt; 0.001) increased resting human T cell phosphatidylinositol hydrolysis and phospholipase C-γ1 phosphorylation. These results indicate that ICAM-3 augments signaling through CD3, functioning as a costimulatory molecule for resting T cells in the initial activation step. J. Leukoc. Biol. 65: 867–874; 1999.
Corticosteroids inhibit the production of inflammatory mediators in immature monocyte-derived DC and induce the development of tolerogenic DC3
Authors: de Jong Esther C , Vieira Pedro L , Kalinski Pawel , Kapsenberg Martien L 
Published: January 2018

Abstract
Corticosteroids (CS) are potent immunosuppressive agents that are known to affect T cell-mediated inflammation by the inhibition of proliferation and cytokine production, as well as the immunostimulatory function of monocytes and macrophages. Not much is known of the effect of corticosteroids on dendritic cells (DC), the professional T cell stimulatory antigen-presenting cells. We report that the endogenous CS hydrocortisone and the synthetic CS clobetasol-17-propionate strongly inhibited the production of the inflammatory mediators interleukin (IL)-12 p70, tumor necrosis factor α (TNF-α), and IL-6 by lipopolysaccharide (LPS)-stimulated monocyte-derived immature DC (iDC) in vitro. In contrast, the stimulatory capacity, antigen uptake, and the expression of costimulatory molecules were not affected. In accordance with the decreased production of IL-12 p70, CS-treated iDC induced less production of the inflammatory Th1 cytokine interferon-γ and enhanced levels of the Th2 cytokines IL-10 and IL-5 in staphylococcal enterotoxin B-stimulated CD4+ Th cells. Furthermore, CS inhibited the maturation of iDC as assessed by the lack of expression of CD83 as well as by the prevention of the loss of antigen uptake capacities. These type 3 DC (DC3) matured in the presence of CS produce less IL-12 p70 and have a decreased T cell stimulatory capacity. Moreover, uncommitted T cells that encounter the CS-induced DC3 develop into Th2-biased cells, which may additionally decrease the Th1-mediated tissue damage but, on the other hand, Th2 cytokines may promote undesirable elevation of IgE and eosinophilia. These findings indicate that suppression of T cell-mediated inflammation by CS not only relies on direct effects on T cells, but also on various effects on DC, their professional antigen- presenting cells. J. Leukoc. Biol. 66: 201–204; 1999.
S100A8: emerging functions and regulation
Authors: Passey Robert J , Xu Ken , Hume David A , Geczy Carolyn L 
Published: January 2018

Abstract
The functional importance of members of the S100 Ca2+-binding protein family is becoming apparent. Murine (m)S100A8 (initially named CP-10) is a potent chemoattractant (10−13 to 10−11 M) for myeloid cells and the chemotactic activity of other S100s has since been reported, suggesting a new class of chemoattractants. Murine S100A8 has been associated with a number of acute and chronic inflammatory conditions including bacterial infection, atherogenesis, and cystic fibrosis. It is expressed constitutively with S100A9 in neutrophils and is regulated by inflammatory stimulants in macrophages and microvascular endothelial cells. The lack of co-expression of S100A9 with S100A8 in activated macrophages suggests distinct functions for the proteins expressed by different cell types. Glucocorticoids up-regulate induction of mS100A8 by inflammatory mediators, and its exquisite sensitivity to oxidation suggests that it may protect against oxidative tissue damage. Inactivation of the mS100A8 gene is embryonic lethal, providing the first evidence for non-redundant function of a member of the S100 gene family. S100A8 may have an immunoregulatory role by contributing to the regulation of fetal-maternal interactions. It may play a protective role and its absence may allow infiltration by maternal cells, a process eventually manifesting as resorption. This review focuses on the variety of emerging functions attributed to murine S100A8, a protein implicated in embryogenesis, growth, differentiation, and immune and inflammatory processes. J. Leukoc. Biol. 66: 549–556; 1999.
The amyloid precursor protein of Alzheimer disease in human brain and blood
Authors: Li Qiao-Xin , Fuller Stephanie J , Beyreuther Konrad , Masters Colin L 
Published: January 2018

Abstract
Studies of the metabolism and function of the amyloid precursor protein (APP) and its proteolytic fragment Aβ in cultured cells, transgenic mice, and post-mortem brain tissue have advanced our understanding of Alzheimer disease (AD). However, the molecular pathogenesis of the disease is still not clear, and we are a long way from finding a cure for the disease. Studies carried out on human platelets and leukocytes have also helped shed light on APP and Aβ metabolism and function. Platelet and leukocyte APP isoforms are processed using mechanisms similar to those in neuronal cells to generate Aβ and soluble forms of APP. The activation of platelets and leukocytes leads to the secretion of APP and Aβ, resulting in higher levels of these proteins in serum. APP and Aβ in the circulation may be involved in the regulation of platelet function and in the modulation of immune responses. Because human platelets and lymphocytes produce all forms of APP and secrete amyloidogenic Aβ peptides, these tissues may be useful in monitoring responses to therapeutic interventions directed at APP metabolism. Although not of neuronal origin, further studies on the more accessible ex vivo tissues, including platelets and leukocytes and other blood components, may reveal potential peripheral markers for AD and will further our understanding of the molecular pathogenesis of AD. J. Leukoc. Biol. 66: 567–574; 1999.
Suppressors of cytokine signaling (SOCS): negative regulators of signal transduction
Authors: Alexander Warren S , Starr Robyn , Metcalf Donald , Nicholson Sandra E , Farley Alison , Elefanty Andrew G , Brysha Marta , Kile Benjamin T , Richardson Rachel , Baca Manuel , Zhang Jian-Guo , Willson Tracy A , Viney Elizabeth M , Sprigg Naomi S , Rakar Steven , Corbin Jason , Mifsud Sandra , DiRago Ladina , Cary Dale , Nicola Nicos A , Hilton Douglas J 
Published: January 2018

Abstract
SOCS-1 was originally identified as an inhibitor of interleukin-6 signal transduction and is a member of a family of proteins (SOCS-1 to SOCS-7 and CIS) that contain an SH2 domain and a conserved carboxyl-terminal SOCS box motif. Mutation studies have established that critical contributions from both the amino-terminal and SH2 domains are essential for SOCS-1 and SOCS-3 to inhibit cytokine signaling. Inhibition of cytokine-dependent activation of STAT3 occurred in cells expressing either SOCS-1 or SOCS-3, but unlike SOCS-1, SOCS-3 did not directly interact with or inhibit the activity of JAK kinases. Although the conserved SOCS box motif appeared to be dispensable for SOCS-1 and SOCS-3 action when over-expressed, this domain interacts with elongin proteins and may be important in regulating protein turnover. In gene knockout studies, SOCS-1−/− mice were born but failed to thrive and died within 3 weeks of age with fatty degeneration of the liver and hemopoietic infiltration of several organs. The thymus in SOCS-1−/− mice was small, the animals were lymphopenic, and deficiencies in B lymphocytes were evident within hemopoietic organs. We propose that the absence of SOCS-1 in these mice prevents lymphocytes and liver cells from appropriately controlling signals from cytokines with cytotoxic side effects. J. Leukoc. Biol. 66: 588–592; 1999.
α9β1 Integrin is expressed on human neutrophils and contributes to neutrophil migration through human lung and synovial fibroblast barriers
Authors: Shang Terry , Yednock Ted , Issekutz Andrew C 
Published: January 2018

Abstract
Accumulation of leukocytes in inflamed tissue involves their migration through vascular endothelium and then in the connective tissue. Recently we utilized a barrier of human synovial, dermal, and lung fibroblasts (HSF, HDF, and HLF) grown on polycarbonate filters as a model of human polymorphonuclear leukocyte (PMN) migration through connective tissue. The β2 integrins (CD11/CD18) and α4, α5, and α6β1 (VLA-4, -5, and -6) integrins each contributed to this PMN migration. Here we report that on human blood leukocytes, α9β1 (VLA-9) is expressed only on PMNs and that it is up-regulated after PMN activation. Based on monoclonal antibody (mAb) blocking studies, α9β1 integrin contributed to C5a-induced PMN migration through fibroblast (HLF and HSF) barriers. This role was apparent only when alternate mechanisms such as CD18, α4, α5, and α6β1 integrins were blocked and then mAb to α9β1 integrin inhibited the residual PMN migration (by 40–50%) through the HLF or HSF barrier, resulting in ≥75% inhibition overall. In contrast, PMN migration across interleukin-1-activated endothelium (HUVEC) in response to a C5a gradient, which is partly (30–40%) via CD11/CD18-independent mechanisms, was not inhibited by adhesion blocking by mAbs to α4, α5, α6, and α9β1 even in combination. These results indicate that α9β1 integrin on PMN may have a special role, in conjunction with other β1 integrins, in mediating PMN migration in the extravascular space, and may contribute to differential neutrophil function within tissues. J. Leukoc. Biol. 66: 809–816; 1999.
Transforming growth factor β from multiple myeloma cells inhibits proliferation and IL-2 responsiveness in T lymphocytes
Authors: Cook Gordon , Campbell John D M , Carr Christine E , Boyd Kelly S , Franklin Ian M 
Published: January 2018

Abstract
Multiple myeloma (MM) is a cancer of plasma cells, characterized by profound suppression of host immune responses. Here we show that MM cell lines significantly suppress the proliferation, blasting, response to interleukin-2 (IL-2), and expression of CD25 by concanavalin A (Con A)-activated or allostimulated peripheral blood T lymphocytes. T cells arrest in the G1 stage of the cell cycle, and do not enter the IL-2 autocrine growth pathway. T cell inhibition was mediated by a soluble factor. MM cell lines did not produce IL-10 but did produce large amounts of transforming growth factor β1 (TGF-β1). T cells were assessed for their ability to respond to IL-2 when co-cultured with MM cells in the presence or absence of the TGF-β inhibitor, TGF-β latency-associated peptide (LAP). MM cells suppressed IL-2 responses but this inhibition was completely reversed by TGF-β LAP. A CD25−, IL-2-dependent blast cell line was not inhibited by MM cells or rhTGF-β, confirming the specificity of the inhibition mechanism for the IL-2 autocrine growth pathway. We conclude that MM cells suppress T cells in their entry into the autocrine IL-2/CD25 pathway and in response to IL-2, and that TGF-β has a significant role to play. J. Leukoc. Biol. 66: 981–988; 1999.