Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of staphylococcal enterotoxin B (SEB), a Staphylococcus aureus-derived bacterial superantigen, on expression of intercellular adhesion molecule-1 (ICAM-1) were examined in cultured normal and transformed (DJM-1 cells) human keratinocytes by flow cytometry, confocal microscopy, digital image processing, and reverse transcriptase-polymerase chain reaction. SEB significantly upregulated ICAM-1 expression in the interferon-gamma (IFN-gamma)-pretreated, HLA-DR-positive normal keratinocytes and DJM-1 cells in a dose-dependent manner, but not in the untreated, HLA-DR-negative cells. Other toxins such as diphtheria and pertussis toxins did not have the effect. The distribution of SEB and HLA-DR molecules was identical on the IFN-gamma-treated, HLA-DR-positive DJM-1 cells by confocal microscopy. Digital image processing analysis demonstrated that SEB induced a transient increase of intracellular calcium concentration only in the IFN-gamma-treated DJM-1 cells. Pretreatment of the IFN-gamma-treated DJM-1 cells with anti-major histocompatibility complex class II monoclonal antibody completely blocked the effect of SEB. Furthermore, ICAM-1 mRNA was detected in the IFN-gamma-pretreated, SEB-exposed normal keratinocytes by reverse transcriptase-polymerase chain reaction. Our results demonstrate that SEB binds to keratinocytes, presumably via major histocompatibility complex class II molecules such as HLA-DR, triggers calcium mobilization, and induces the synthesis of ICAM-1 molecules. We speculate that, in various cutaneous disorders, SEB penetrates the epidermis and interacts with HLA-DR-positive keratinocytes to upregulate ICAM-1 expression, thus modulating the course of the inflammatory process.
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PMID:Staphylococcal enterotoxin B upregulates expression of ICAM-1 molecules on IFN-gamma-treated keratinocytes and keratinocyte cell lines. 756 Nov 55

In a model of vasculitis we have evaluated mechanisms for how neutrophil polymorphonuclear granulocytes (PMNs) kill cultured human umbilical vein endothelial cells (HUVECs) in vitro (as release of chromium 51) in response to the double dioxygenation product of arachidonic acid, lipoxin A4 (LXA4) and to formyl-methionyl-leucyl-phenylalanine (fMLP). The cytolysis induced by LXA4 and fMLP was dose dependent, with maximum values at 100 nmol/L (which caused a 2.7-fold and 2.3-fold increases of 51Cr release, respectively, relative to buffer-treated controls). LXA4 also conferred a peak of cytotoxicity at 0.1 nmol/L (which caused a 2.2-fold increase in 51Cr release). Leukotriene B4, platelet activating factor (PAF), and zymosan-activated serum were inefficient. Phorbol myristate acetate caused the most prominent cytotoxicity, which was first evident at 1 mumol/L. The LXA4 effect was abrogated by superoxide dismutase, catalase, alpha 2-macroglobulin, and alpha 1-antitrypsin but not by mannitol. Addition of a monoclonal antibody (mAb) to CD18 also inhibited neutrophil-dependent cytotoxicity to LXA4 and fMLP. MAbs to intercellular adhesion molecule-1 or P-selectin blocked 100% and 52%, respectively, of the LXA4-induced cytotoxicity. Neutrophils from a patient with chronic granulomatous disease were incapable of mediating any cytotoxicity. The LXA4 effect was inhibited by the PAF receptor antagonist WEB-2086 and by treating neutrophils with pertussis toxin. Thus this novel effect of LXA4, as a potent promoter of neutrophil-mediated cytotoxicity for HUVECs, is a process dependent on PMN adhesion proteins, oxygen radicals, and proteases, and it is apparently associated with endogenous PAF expression and requires pertussis-sensitive G proteins.
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PMID:Mechanisms for lipoxin A4-induced neutrophil-dependent cytotoxicity for human endothelial cells. 760 32

An important interplay exists between specific viral respiratory infections and altered airway responsiveness in the development and exacerbations of asthma. However, the mechanistic basis of this interplay remains to be identified. This study addressed the hypothesis that rhinovirus (RV), the most common viral respiratory pathogen associated with acute asthma attacks, directly affects airway smooth muscle (ASM) to produce proasthmatic changes in receptor-coupled ASM responsiveness. Isolated rabbit and human ASM tissue and cultured ASM cells were inoculated with human RV (serotype 16) or adenovirus, each for 6 or 24 h. In contrast to adenovirus, which had no effect, inoculation of ASM tissue with RV induced heightened ASM tissue constrictor responsiveness to acetylcholine and attenuated the dose-dependent relaxation of ASM to beta-adrenoceptor stimulation with isoproterenol. These RV-induced changes in ASM responsiveness were largely prevented by pretreating the tissues with pertussis toxin or with a monoclonal blocking antibody to intercellular adhesion molecule-1 (ICAM-1), the principal endogenous receptor for most RVs. In extended studies, we found that the RV-induced changes in ASM responsiveness were associated with diminished cAMP accumulation in response to dose-dependent administration of isoproterenol, and this effect was accompanied by autologously upregulated expression of the Gi protein subtype, Gialpha3, in the ASM. Finally, in separate experiments, we found that the RV-induced effects on ASM responsiveness were also accompanied by autologously induced upregulated mRNA and cell surface protein expression of ICAM-1. Taken together, these findings provide new evidence that RV directly induces proasthmatic phenotypic changes in ASM responsiveness, that this effect is triggered by binding of RV to its ICAM-1 receptor in ASM, and that this binding is associated with the induced endogenously upregulated expression of ICAM-1 and enhanced expression and activation of Gi protein in the RV-infected ASM.
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PMID:Mechanism of rhinovirus-induced changes in airway smooth muscle responsiveness. 980 87

F(2)-Isoprostanes are generated from a cyclooxygenase-independent oxidative modification of arachidonic acid. They are present in atherosclerotic plaques and are platelet activators as well as potent vasoconstrictors. Polymorphonuclear neutrophils are major players in ischemia/reperfusion injury and in restenosis after PTCA. The effects of 8-isoprostaglandin (PG) F(2alpha) on very rapid beta(2)-integrin-dependent adhesion was evaluated in human neutrophils in vitro by use of purified integrin as ligand. 8-Iso-PGF(2alpha) (1 nmol/L to 20 micromol/L) triggers a dose-dependent, very rapid neutrophil adhesion to human fibrinogen but not to the endothelial ligand intercellular adhesion molecule-1. Pretreatment with anti-ss(2)-integrin subtypes showed activation of CD11b/CD18 and CD11c/CD18. Adhesion triggering was completely prevented by pertussis toxin. SQ29,548, a specific antagonist of thromboxane A2 receptor, also dose-dependently prevented 8-iso-PGF(2alpha)-triggered neutrophil adhesion. 8-Iso-PGF(2alpha) did not trigger adhesion in human monocytes and lymphocytes and did not induce neutrophil chemotaxis or activation of the oxygen free-radical-forming enzyme NADPH-oxidase. These data highlight the role of 8-iso-PGF(2alpha) as a specific activator of rapid neutrophil adhesion and suggest its involvement in the pathogenesis of ischemia/reperfusion injury and in restenosis after PTCA. The effect is transduced via activation of the receptor for thromboxane A2.
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PMID:8-Iso-PGF2 alpha induces beta 2-integrin-mediated rapid adhesion of human polymorphonuclear neutrophils: a link between oxidative stress and ischemia/reperfusion injury. 1114 33

T cells that emigrate from the thymus have primarily been studied in vivo using fluorescent dye injection of the thymus. This study examined the properties of thymocytes that emigrate from cultured thymic lobes in organ culture. Under these conditions, thymic emigrants displayed the expected phenotype, that of mature thymocytes expressing high levels of T-cell receptor (TCR-alphabeta) and either CD4 or CD8, and were observed to emigrate within 24 hours of positive selection. Emigration was inhibited by cytochalasin D, pertussis toxin, or Clostridium difficile toxin B, implicating an active motility process. Most of the surface markers on alphabeta-thymic emigrants (Thy1, CD44, CD69, CD25, leukocyte functional antigen-1, intercellular adhesion molecule-1, alpha(4)-integrin, alpha(5)-integrin, CD45, and CD28) were expressed at a surface density similar to that on mature intrathymic cells and peripheral splenic T cells. Heterogeneous expression of L-selectin and heat-stable antigen (HSA) suggested that subsets emerge from the thymus with a commitment to different migration patterns. The only marker on emigrants not found on either intrathymic cells or mature spleen T cells was CTLA-4, which could dampen the response of emigrants to peripheral antigens. Antigen responsivenes measured in vitro against allogeneic dendritic cells showed a proliferative response comparable to that of splenic T cells. In vivo, however, thymic emigrants failed to induce an acute graft-versus-host reaction in allogeneic severe combined immunodeficiency recipients. This suggests that a mechanism operating in vivo, perhaps tolerance or migration pattern, attenuates the response of emigrants against antigens that did not induce their deletion in the thymus.
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PMID:Thymic emigrants isolated by a new method possess unique phenotypic and functional properties. 1122 81

In a reconstituted flow chamber system, preincubation with chemokines can trigger the arrest of rolling monocytes, suggesting that this interaction could help recruit these cells to early atherosclerotic lesions. To date, however, the contribution of endothelium-derived chemokines found in these lesion to monocyte arrests has not been investigated. The endothelium of lesion-prone carotid arteries from apolipoprotein E-deficient (ApoE(-/-)) mice, but not control mice, presents the chemokines KC (mouse GRO-alpha) and JE (mouse monocyte chemoattractant protein-1 [MCP-1]). Arrest of a monocytic cell line or mouse blood monocytes perfused through carotid arteries of ApoE(-/-) mice was reduced by treating with either pertussis toxin, an antagonist of CXCR2, or an antibody to KC, but this process was insensitive to agents that blocked CCR-2 or JE. Conversely, monocyte accumulation more than doubled upon pre-perfusion of the carotid artery with KC but not with mouse MCP-1. Blockade of alpha(4)beta(1) integrin (VLA-4) or vascular cell adhesion molecule-1, but not CD18 or intercellular adhesion molecule-1, almost completely inhibited the arrest of monocytes. We conclude that when presented by early atherosclerotic lesions, KC but not murine MCP-1 triggers VLA-4-dependent monocyte recruitment.
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PMID:The chemokine KC, but not monocyte chemoattractant protein-1, triggers monocyte arrest on early atherosclerotic endothelium. 1169 68

Monocyte chemoattractant protein-1 (MCP-1) is a potent chemokine synthesized by several cell types, e.g., inflammatory cells, such as monocytes, and resident renal cells, such as human tubular epithelial cells (TECs). Besides induction of monocyte recruitment, MCP-1 has been suggested to induce non-leukocytes to produce cytokines and adhesion molecules. Inflammation of the tubulointerstitium is a hallmark of many renal diseases and contributes to progression of renal failure; the purpose therefore of this study was to investigate the influence of MCP-1 on markers of inflammatory activation in human TECs. MCP-1 stimulated interleukin-6 (IL-6) secretion and intercellular adhesion molecule-1 (ICAM-1) synthesis in a time- and dose-dependent manner. In parallel, MCP-1 increased IL-6 and ICAM-1 mRNA expression in human TECs. Pretreatment with pertussis toxin, GF109203X, BAPTA-AM, and pyrrolidine dithiocarbamate inhibited MCP-1-dependent IL-6 and ICAM-1 synthesis, suggesting the involvement of Gi-proteins, protein kinase C, intracellular Ca(2+), and nuclear factor-kappaB (NF-kappaB) in MCP-1 signaling. Using electrophoretic gel mobility shift assay, we observed that MCP-1 stimulated binding activity of NF-kappaB. Binding activity of the activator protein-1 (AP-1), which has been implicated to regulate induction of the IL-6 gene together with NF-kappaB, was also stimulated by MCP-1. In the present experiments, NF-kappaB and AP-1 were involved in the MCP-1-mediated induction of IL-6, as demonstrated by cis element double-stranded (decoy) oligonucleotides (ODN). In contrast to IL-6 release, MCP-1-induced ICAM-1 expression was predominantly dependent on NF-kappaB activation. These results document for the first time that MCP-1 induces an inflammatory response in human TECs. This may be an important new mechanism in the pathogenesis of tubulointerstitial inflammation.
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PMID:MCP-1 induces inflammatory activation of human tubular epithelial cells: involvement of the transcription factors, nuclear factor-kappaB and activating protein-1. 1203 83

Adhesion molecules on respiratory epithelial cells play a critical role in inflammatory cell recruitment and accumulation at sites of inflammation. Bordetella pertussis colonizes the human respiratory tract by infecting epithelial cells, leading to an inflammatory response. In this study, the role of bacterial factors in the expression of intercellular adhesion molecule-1 (ICAM-1) on human respiratory epithelial cells was investigated in response to B. pertussis. Flow cytometry and real time RT-PCR analysis showed that BEAS-2B human bronchial epithelial cells expressed increased levels of ICAM-1 mRNA and surface protein in response to B. pertussis infection. Filamentous hemagglutinin (FHA) played a role in this response because of the impaired capability of a FHA-deficient isogenic strain. A mutant strain in which an Arg-Gly-Asp (RGD) site of FHA had been changed to Arg-Ala-Asp had diminished ability to up-regulate ICAM-1 expression. RGD sequence-associated up-regulation of ICAM-1 expression was also observed in primary normal human bronchial epithelial cells. Pretreatment of cells with integrin antagonists such as RGD-containing peptide and antibody against very late antigen-5 (VLA-5) inhibited the up-regulation of ICAM-1 expression, suggesting the participation of VLA-5 integrin in this response. Pertussis toxin (PT) prevented the up-regulation of ICAM-1 expression because a PT-deficient mutant strain induced higher levels of ICAM-1 mRNA and surface protein than the parental strain. Consistent with this, purified PT suppressed the up-regulation of epithelial ICAM-1 expression. These findings demonstrate that B. pertussis FHA up-regulates ICAM-1 expression on respiratory epithelial cells through interaction of its RGD site with host cell VLA-5 integrin, and that PT impairs this response.
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PMID:Bordetella pertussis infection of human respiratory epithelial cells up-regulates intercellular adhesion molecule-1 expression: role of filamentous hemagglutinin and pertussis toxin. 1222 Sep 88

We previously reported that murine experimental allergic encephalomyelitis can be induced by an additional intraperitoneal and intracerebral (i.c.) restimulation in resistant B6 mice after standard immunization with myelin antigens in complete Freund's adjuvant and Bordetella pertussis coadjuvant. Neutrophils infiltrated into perivascular spaces at 12 h, followed by mononuclear cells 24 h after i.c. injection. In this study, we report that the i.c. injection induced the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). The kinetic expression of ICAM-1 or VCAM-1 on brain endothelial cells paralleled the infiltration of neutrophils and mononuclear cells, respectively. The infiltrated lymphocytes also expressed very late antigen-4 (VLA-4) molecules. The microvascular endothelial cells were positive for VCAM-1, whereas the surrounding mononuclear cells were VLA-4 positive. Furthermore, we found a unique subpopulation of cells with characteristics of CD4(-)CD8(-)V(beta)8(+) markers. The kinetic studies of this population showed that these cells were transiently depleted from 12 to 24 h after i.c. challenge (before the development of clinical symptoms) in cervical lymph nodes. These CD4(-)CD8(-)V(beta)8(+) cells can be expanded by in vitro culture with myelin basic protein or IL-2. No significant changes of CD4(+)/CD8(+) cells were noted. CD4(+)CD8(-)CD3(+) cells were also found in brain by double histochemical stains and were the major infiltrating cells at 24 or 48 h after i.c. challenge.
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PMID:Infiltrated Cells in Experimental Allergic Encephalomyelitis by Additional Intracerebral Injection in Myelin-Basic-Protein-SensitizedB6 Mice. 1238 77

Adhesion molecules and C-C chemokines play an important role in the accumulation of eosinophils in allergic inflammation. In the present study, the expression and function of adhesion molecules on eosinophils from asthmatic patients and involvement of RANTES and eotaxin were examined. Eosinophils isolated by the CD16 negative selection method were stimulated with or without RANTES or eotaxin. Expression of b integrins on eosinophils and the functional adherence to recombinant soluble intercellular adhesion molecule-1 (r-sICAM-1)-coated plates were examined. Compared with normal subjects, eosinophils from asthmatic patients showed increased expression of b2 integrins and functional adherence to r-sICAM-1-coated plates. RANTES and eotaxin augmented the functional adherence of eosinophils without a significant upregulation of b2 integrins. Anti-b2 integrin antibody inhibited the augmentative effect on eosinophil adherence of RANTES and eotaxin. Pertussis toxin, wortmannin, and genistein inhibited chemokine-induced adherence. RANTES and eotaxin are closely related to eosinophil accumulation not only as chemotactic agents but also as augmentative agents for eosinophil adherence through involvement in functional eosinophil adherence to ICAM-1 by a possible qualitative change of b2 integrins. Pertussis toxin-sensitive G proteins, PI3 kinase, and tyrosine kinase are involved in signal transduction leading to activation of b2 integrins on eosinophil following stimulation with RANTES and eotaxin.
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PMID:Possible involvement of C-C chemokines in functional augmentation of adhesion molecules in asthmatic patients. 1248 19


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