ISSN:0741-5400    

DOI:10.1002/jlb.58.2.119

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractCellular immune responses depend on regulated pathways of intracellular signal transduction and leukocyte activation. Although these mechanisms are coordinated by a variety of leukocyte‐restricted effector molecules, recent observations have uncovered a novel role of proteases in transducing outside‐in signals of leukocyte activation. Through regulated, receptor‐mediated recognitions, coagulation and fibrinolytic enzymes or effector cell granular proteases influence monocyte motility and chemotaxis, modulate pleiotropic cytokine responses, contribute to mononuclear cell proliferation, or induce target cell apoptosis. Overall, these mechanisms define a novel interface between general inflammatory reactions, invariably characterized by activation of blood protease cascades, and specialized aspects of cellular immune functions.J. Leukoc. Biol.58: 120–127; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.58.2.120

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractGene‐encoded peptide antibiotics are ubiquitous components of host defenses in mammals, birds, amphibia, insects, and plants. Their de novo synthesis or release from storage sites can be induced rapidly, which makes them particularly important in the initial phases of resistance to microbial invasion. The endogenous antimicrobial peptides of animals are products of single genes and are synthesized as preproproteins. Multistep processing yields the mature peptide, which generally acts by inducing microbial membrane permeabilization. Several families of antimicrobial peptides have been identified that differ with respect to the presence of disulfide linkages, amino acid composition, structural conformation, and spectrum of activity. The arginine‐rich three disulfide‐containing β‐βheet defensins are remarkably abundant and widely distributed in animals and plants. The antibiotic peptides of higher eukaryotes merit further study for their role in natural immunity and their potential as novel therapeutic compounds.J. Leukoc. Biol.58: 128–136; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.58.2.128

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractOrganisms respond to infection with complex adaptations involving bidirectional communication between the immune and neuroendocrine systems. The idea of intercellular communication between the neuroendocrine and immune systems via common signal molecules has provided a conceptual framework for such crosstalk. The studies to date show that cells of the immune system contain receptors for neuroendocrine hormones and can also be considered a source of pituitary and hypothalamic peptides. The structure and pattern of synthesis of these peptides by leukocytes appear similar to neuroendocrine hormones, although some differences exist. Once secreted, these peptide hormones may function as endogenous regulators of the immune system as well as conveyors of information from the immune to the neuroendocrine system. The plasma hormone concentrations contributed by lymphocytes usually do not reach the levels required when the pituitary gland is the source, but because immune cells are mobile, they have the potential to locally deposit the hormone at the target site. Likewise, other studies show that cells of the neuroendocrine system contain receptors for cytokines and can also be considered a source of cytokines, particularly interleukin‐1 (IL‐1) and IL‐6. In the pituitary IL‐1β coexists with thyroid stimulating hormone in a subpopulation of thyrotropes, suggesting it may have a role as a pituitary paracrine factor. The cytokines, including IL‐1, IL‐2, EL‐6, interferon‐γ, and tumor necrosis factor, exert profound effects on hypothalamic pituitary axes. It is our hypothesis that the relay of information to the neuroendocrine system represents a sensory function for the immune system wherein leukocytes recognize stimuli that are not recognizable by the central and peripheral nervous systems (i.e., bacteria, tumors, viruses, and antigens). The recognition of such noncognitive stimuli by immunocytes is then converted into information and a physiological change occurs. Future studies into the physiological role that cytokines and neuroendocrine hormones have in these systems will be of considerable interest for both immunologists and endocrinologists.J. Leukoc. Biol.57: 137–150; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.58.2.137

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractMurine reconstitution assays were used to investigate the effects of recombinant human interleukin‐7 (rhIL‐7) on myeloid and lymphoid precursors and on bone marrow engraftment. Reconstitution with bone marrow from rhIL‐7‐treated mice results in a 3.4‐fold decrease in total colony‐forming unit‐spleen (CFU‐S) activity (day 9) and an 18.1‐ and 11.9‐fold decrease in its ability to generate thymocytes and splenic B lineage cells, respectively. In contrast, after reconstitution with splenocytes from rhIL‐7‐treated mice, CFU‐S activity increased 23.6‐fold (day 9) and the thymocyte and splenic B lineage cell regenerative capacity increased by 4.0‐ and 3.2‐fold, respectively. In addition, CD43low+, B220low+cells that contain pre‐pro‐B cells and pro‐B cells were expanded two‐ to threefold and Igμ‐, B220+, CD2‐and Igμ‐, B220+, CD2+B lineage cells were expanded approximately 10‐fold and 10‐ to 45‐fold (depending on the tissue examined), respectively, after rhIL‐7 treatment Administration of rhIL‐7 to irradiated mice transplanted with bone marrow resulted in accelerated T cell and B cell reconstitution by up to 2–4 weeks. Thus, rhIL‐7 administration affects the distribution of myeloid and lymphoid precursors. Moreover, rhIL‐7 administration accelerates murine bone marrow cell engraftment and therefore may be useful in reducing the engraftment time in bone marrow transplant patients.J. Leukoc. Biol.58: 151–158; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.58.2.151

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractModulation of burn‐associated CD8+CD11b+T cell receptorγ/δ+suppressor T cells (BA2T cells) and improved resistance to herpesvirus infections was studied in thermally injured mice. The susceptibility of thermally injured mice to infection by herpes simplex virus (HSV) was approximately 100 times greater than it was in normal mice. The increased susceptibility of thermally injured mice to HSV infection was transferred to normal mice by BA2T cells, which appeared in spleens of mice 2–9 days after thermal injury. The suppressor cell activity of BA2T cells was effectively counteracted by CD4+CD28+T cell receptorα/β+Vicia villosalectin adherent antisuppressor cells (designated as bum‐induced contrasuppressor T cells; BCS cells), which were generated naturally in spleens of mice after the appearance of BA2T cells. The adoptive transfer of BCS cells to mice just after the injury improved the resistance of thermally injured mice to HSV infection to levels observed in normal mice. These results suggest that the increased susceptibility of thermally injured mice to HSV infection may be affected by BA2T suppressor cells and BCS cells may improve the resistance of thermally injured mice to HSV infection through the inhibition of BA2T suppressor cell activities.J. Leukoc. Biol.58: 159–167; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.58.2.159

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractComplement protein C1q induces the production of superoxide (O2‐) by neutrophils via an as yet unidentified receptor or receptor complex. Several strategies were therefore used to identify cell surface molecules involved in the response of neutrophils to C1q and its collagen‐like domain (C1q‐CLR). Treatment of neutrophils with phosphatidylinositol‐specific phospholipase C effectively removed the phosphatidylinositol‐linked surface molecules CD14 and CD16, yet did not reduce Of production in response to C1q. Next, 17 monoclonal antibodies (mAbs) recognizing various neutrophil surface antigens were tested for their ability to inhibit C1q‐CLR‐mediated O2‐production. Only two of the mAbs, 44a and IB4, which recognize CD11b/CD18 (complement receptor 3 or Mac‐1), were inhibitory. In addition, neutrophils from a patient with leukocyte adhesion deficiency, which are CD18 deficient, did not produce Of in response to C1q or C1q‐CLR. Because CD11b/CD18 is recognized to play a role in cell adhesion, the role of adherence in C1q‐mediated O2‐production was explored. Adherence of neutrophils to C1q‐CLR‐coated surfaces occurred with kinetics, which usually paralleled those of O2‐production, and was invariably abolished by the anti‐CD11b mAb 44a. However, this mAb often only partially inhibited O2‐production, indicating that an avid attachment of neutrophils to the C1q‐CLR‐coated surface is not required for O2‐production.J. Leukoc. Biol.58: 168–176; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.58.2.168

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractHuman basophils, stimulated with either anti‐IgE antibody or formyl‐methionine‐leucine‐phenylalanine, were examined by two measures of the cell response that may reflect degranulation. Flow cytometric measurement of either of these two measures, changes in forward scatter intensity (an indirect measure of the basophil size) or changes in the intensity of acridine orange‐loaded cells (which labels basophil granules), allowed an assessment of the distribution of single cell responses. With regard to the latter technique, structures that appeared to be basophil granules were shown to metachromatically label with low concentrations of acridine orange, which has little or no effect on histamine release. During stimulation these labeled granules were lost, leading to decreased fluorescence. Changes in either the forward scatter parameter or acridine orange labeling occurred on the same time scale as histamine release, differentiating these measures of the basophil response from early signal transduction events. Challenging basophils with a combination of phorbol myristate acetate and ionomycin caused 100% histamine release and allowed a measurement of the maximum change in forward scatter intensity or loss of acridine orange labeling. The flow cytometric distributions after this treatment were then compared with the distributions obtained by challenging cells with several concentrations of anti‐IgE antibody or formyl‐methionine‐leucine‐phenyialanine, which induced various submaximal responses. These flow cytometric distributions demonstrated that single cells could be found in intermediate states of activation, i.e., the response of all cells was graded according to the strength of the stimulus. These studies lead to the general conclusion that all aspects of the basophil response, including those late events in the basophil response we have studied here, as well as early events that we have studied previously, are graded in a continuous manner, according to the magnitude of the stimulus.J. Leukoc. Biol.58: 177–188; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.58.2.177

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractThis study was undertaken to examine the mechanisms involved in polymorphonuclear leukocyte superoxide release stimulated by exogenous phosphatidic acid (PA). Unlike the immediate burst of superoxide release affected by membrane‐permeable dioctanoyl‐glycerol (DiC8‐DAG), dioctanoyl phosphatidic acid (DiC8‐PA) induced superoxide release after a lag period of 5–20 min. This period was considerably reduced or eliminated when cells were primed by substimulatory levels of phorbol myristate acetate (PMA). Granule‐depleted neutrophil cytoplasts also responded to DiC8‐PA with a burst of superoxide generation. Activation of the cytoplast superoxide generating system in response to DiC8‐PA was also significantly faster after cells had been preexposed to substimulatory levels of PMA, indicating that at least a portion of the priming mechanism was independent of PMA‐induced degranulation. To further examine the potential mechanism of PMA priming of responses to PA, we evaluated the activity of neutrophilecto‐phosphatidic acid phosphohydrolase (ecto‐PA phosphohydrolase), which generates diacylglycerol from exogenous PA. PMA priming had no discernable effect on the activity of this enzyme. In addition, propranolol, an inhibitor of PA phosphohydrolase, did not selectively inhibit PMA priming of neutrophil responses to DiC8‐PA, indicating that priming did not result from acceleration of DiC8‐PA hydrolysis. We therefore investigated the possibility that activation of protein kinase C was the basis of the primed response. Several semiselective protein kinase C inhibitors (calphostin C, H‐7, and acylmethylglycerol) inhibited DiC8‐DAG‐ and DiC8‐PA‐induced superoxide release as well as PMA‐primed responses to approximately the same extent. These results are consistent with the hypothesis that neutrophil responses to phosphatidate are mediated by diglyceride generated by the action ofecto‐PA phosphohydrolase. PMA priming does not result from increased catalytic activity ofecto‐PA phosphohydrolase but rather seems to result from potentiation of an intermediate involved in the cells' response to multiple stimuli.J. Leukoc. Biol.58: 189–195; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.58.2.189

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractIn these studies we provide conclusive evidence that (β/γ) actin present in human neutrophils is a substrate for nitric oxide (NO)‐dependent ADP ribosylation and that this modification is associated with the inhibition of actin polymerization. A 43‐kDa substrate for NO‐dependent ADP ribosylation was identified as actin by four methods: (1) comigration with the botulinum C2 toxin substrate by two‐dimensional gel electrophoresis (pI 5.2), (2) identity between the peptide map generated by V8 protease digestion of the NO and botulinum C2 substrates, (3) immunoprecipitation with antiactin antibodies, and (4) the ability of NO to ADP ribosylate purified neutrophil G‐actin in the presence of plasma membrane cofactors. Because the ADP ribosylation of actin by the botulinum C2 toxin is known to inhibit F‐actin polymerization, we examined the effect of NO on actin assembly. Flow cytometry revealed that NO inhibited formyl‐methionine‐leucine‐phenylalanine (fMLP)‐dependent (SO s at 37°) F‐actin formation (108 ± 8 vs. 89 ± 6 relative fluorescence units,P<.02). These results were confirmed by quantification of F‐actin formation by gel scanning (10% sodium dodecyl sulfate gel, Coomassie, and densitometry): pretreatment of polymorphonuclear leukocytes with NO resulted in a reduction of fMLP‐induced, cytoskeletal‐associated F‐actin, which was accompanied by an increase of Triton‐soluble G‐actin. NO also inhibited F‐actin formation, as observed by means of rhodamine phalloidin staining of neutrophils adherent to a fibronectin‐coated surface. This effect was accompanied by a dose‐dependent inhibition of neutrophil adherence in NO‐treated cells. The data indicate that NO inhibits cytoskeletal assembly and adherence in human neutrophils in association with the ADP ribosylation of actin.J. Leukoc. Biol.58: 196–202; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.58.2.196

出版商:Wiley    

年代:1995

数据来源: WILEY