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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Pertussis toxin binds target cells through the carbohydrate recognition properties of two subunits, S2 and S3, which share amino acid sequence similarity with the lectin domains of the eukaryotic selectin family. Selectins appear on inflamed endothelial cells and promote rolling of leukocytes by reversibly binding carbohydrates. S2, S3, and synthetic peptides representing their carbohydrate recognition domains competitively inhibited adherence of neutrophils to selectin-coated surfaces and to endothelial cells in vitro. These proteins and peptides also rapidly upregulated the function of the leukocyte integrin CD11b/CD18. These findings implicate mimicry of eukaryotic selectins by prokaryotic adhesive ligands and link the mechanisms underlying leukocyte trafficking to microbial pathogenesis.
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PMID:Prokaryotic peptides that block leukocyte adherence to selectins. 768 93

Factor X (factor ten) of the coagulation cascade binds to the integrin CD11b/CD18 during inflammation, initiating procoagulant activity on the surface of leukocytes (Altieri, D.C., O.R. Etingin, D.S. Fair, T.K. Brunk, J.E. Geltosky, D.P. Hajjar, and T. S. Edgington. 1991. Science [Wash.DC]. 254:1200-1202). Filamentous hemagglutinin (FHA), an adhesin of Bordetella pertussis also binds to the CD11b/CD18 integrin (Relman D., E. Tuomanen, S. Falkow, D.T. Golenbock, K. Saukkonen, and S.D. Wright. 1990. Cell. 61:1375-1382). FHA and the CD11b/CD18 binding loops of Factor X share amino acid sequence similarity. FHA peptides similar to Factor X binding loops inhibited 125I-Factor X binding to human neutrophils and prolonged clotting time. In addition, ETKEVDG and its Factor X analogue prevented transendothelial migration of leukocytes in vitro and reduced leukocytosis and blood brain barrier disruption in vivo. Interference with leukocyte migration by a coagulation-based peptide suggests a novel strategy for antiinflammatory therapy.
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PMID:Inhibition of leukocyte-endothelial cell interactions and inflammation by peptides from a bacterial adhesin which mimic coagulation factor X. 788 55

Neutrophil infiltration is a prominent feature of Clostridium difficile-associated enteritis and colitis. The aim of this study was to examine the importance of neutrophil recruitment and neutrophil-mediated tissue damage in C. difficile toxin A-induced enteritis. Competitive binding experiments using purified 3H-toxin A demonstrated the presence of a single class of medium affinity receptors on rabbit neutrophils (Kd 7 x 10(-8) M). Pertussis toxin and the nonhydrolyzable GTP analog GTPgamma S both inhibited 3H-toxin A binding (by 56 and 65%, respectively), indicating that the rabbit neutrophil toxin A receptor is G protein linked. Toxin A elicited a dose-dependent (25-200 micrograms/ml) stimulation of neutrophil migration in vitro, and this functional effect was also pertussis toxin sensitive (69% inhibition). Treatment of neutrophils with R15.7, a blocking monoclonal antibody to the leuocyte adhesion molecule CD18, inhibited toxin A-stimulated neutrophil migration by 85% in vitro. Pretreatment of rabbits with R15.7 also prevented neutrophil infiltration of toxin A-exposed ileal loops in vivo as determined by histologic examination and by ileal tissue myeloperoxidase levels. Furthermore, R15.7 effected a substantial inhibition of fluid secretion (by 65%), mannitol permeability (by 66%), and histologic damage in toxin A-exposed ileal loops. Anti-CD18 (R15.7) had no inhibitory effect on cholera toxin enterotoxicity. These data demonstrate that C. difficile toxin A is a proinflammatory toxin whose enterotoxic effects are substantially dependent upon neutrophil recruitment.
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PMID:Neutrophil recruitment in Clostridium difficile toxin A enteritis in the rabbit. 790 3

Bordetella pertussis, the causative agent of whooping cough, adheres to human monocytes/macrophages by means of a bacterial surface-associated protein, filamentous hemagglutinin (FHA) and the leukocyte integrin, complement receptor 3 (CR3, alpha M beta 2, CD11b/CD18). We show that an FHA Arg-Gly-Asp site induces enhanced B. pertussis binding to monocytes, and that this enhancement is blocked by antibodies directed against CR3. Enhancement requires a monocyte signal transduction complex, composed of leukocyte response integrin (alpha? beta 3) and integrin-associated protein (CD47). This complex is known to upregulate CR3 binding activity. Thus, a bacterial pathogen enhances its own attachment to host cells by coopting a host cell signaling pathway.
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PMID:Bordetella pertussis filamentous hemagglutinin interacts with a leukocyte signal transduction complex and stimulates bacterial adherence to monocyte CR3 (CD11b/CD18). 793 Oct 59

In these studies we show that stimulation of O2- generation by Tumor necrosis factor-alpha (TNF), or antibodies against the common beta 2 chain of leukocyte integrins (CD18), or LFA-1 (CD11a) displays a common and unique pattern of sensitivity or insensitivity to inhibitors of different signalling pathways. Both ways of stimulating neutrophil O2- generation were blocked by wortmannin, an inhibitor of myosin light chain kinase (Nakanishi, S., et al., 1992., J. Biol. Chem. 267, 2157-2163), and three different inhibitors of protein tyrosine kinases. Neither staurosporine, a protein kinase C inhibitor, nor Pertussis toxin, at concentrations which inhibited O2- generation in response to PMA, and FMLP, respectively, had any effect.
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PMID:Effect of inhibitors of distinct signalling pathways on neutrophil Q2- generation in response to tumor necrosis factor-alpha, and antibodies against CD18 and CD11a: evidence for a common and unique pattern of sensitivity to wortmannin and protein tyrosine kinase inhibitors. 809 58

The leukocyte adhesion molecule CR3 (CD11b/CD18, Mac-1) promotes leukocyte transmigration into tissues by engaging an unknown cognate ligand on the surface of vascular endothelial cells. Filamentous hemagglutinin (FHA), an adhesin of the bacterium Bordetella pertussis, binds to CR3. We hypothesized that FHA mimics the native ligand for the CR3 integrin on endothelial cells and predicted that anti-FHA antibodies should bind to endothelial cells, interfere with leukocyte recruitment, and induce endothelial permeability. Anti-FHA monoclonal antibodies bound to cerebral microvessels in sections from human brain and upon intravenous injection into rabbits. Antibody binding correlated with the ability to recognize two polypeptides in extracts of human cerebral vessels that were also bound by CD18. In vivo, antibody binding not only interfered with transmigration of leukocytes into cerebrospinal fluid but also induced a dose-dependent reversible increase in blood-brain barrier permeability sufficient to improve delivery of intravenously administered therapeutic agents to brain parenchyma.
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PMID:Reversible opening of the blood-brain barrier by anti-bacterial antibodies. 810 2

The molecular basis for direct bacteria-macrophage interactions that distinguishes nontypeable (NT) Haemophilus influenzae from type b organisms is not known. Because of similarities between filamentous hemagglutinin (FHA) adhesin of Bordetella pertussis and high-molecular-weight (HMW) proteins commonly expressed by NT H. influenzae, the role that HMW proteins play in determining NT H. influenzae-macrophage interactions was assessed. In tests with genetically engineered organisms, HMW protein-expressing bacteria bound significantly better than isogenic HMW protein-deficient bacteria to macrophages. HMW protein-dependent binding to macrophages is trypsin-sensitive, is independent of divalent cations, does not occur via the leukocyte integrin CD11b/CD18, and is not affected by galactose-containing carbohydrates. Organisms bound via HMW proteins remain largely extracellular and viable. Like FHA of Bordetella organisms, HMW proteins mediate binding of NT H. influenzae to macrophages. However, unlike the interaction determined by FHA, this interaction is characteristically one of adhesion and requires additional serum opsonization for efficient killing of bacteria by macrophages.
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PMID:High-molecular-weight surface-exposed proteins of Haemophilus influenzae mediate binding to macrophages. 810 76

The CD11/CD18 family of leukocyte glycoproteins is essential in the process of adherence to endothelial and other cells that occurs during the acute inflammatory response. The cell surface expression of one member of this family, CD11b/CD18, or Mac-1, is increased on monocytes, neutrophils and other cell types by a number of agents, including chemotactic peptides and lipid mediators. The intracellular signalling mechanisms which control Mac-1 expression are not fully understood. In this report we have investigated the role of G proteins and extracellular Ca2+ in the stimulation of Mac-1 upregulation by the chemoattractant C5a in the human monocyte-like cell line, U937. Two signal transduction pathways are apparently involved and can be distinguished by their sensitivity to pertussis toxin, which inhibits activation of the Gi class of G proteins. The results indicate that a pertussis toxin-insensitive influx of extracellular Ca2+ may be one part of a network of signals leading to Mac-1 upregulation on U937 cells. This is in contrast to the stimulation of this process in neutrophils by chemotactic peptide, which is reported to be entirely dependent on pertussis toxin sensitive G proteins and independent of extracellular Ca2+.
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PMID:Multiple signalling pathways in the C5a-induced expression of adhesion receptor Mac-1. 816 55

We investigated the effects of hypoxia/reoxygenation (H/R) and subsequent stimulation of polymorphonuclear leukocytes (PMNs) with either formyl-methionyl-leucyl-phenylalanine (FMLP) or phorbol myristate acetate (PMA) on CD32, CD16, CD35, and CD11b/CD18 expression and on degranulation and superoxide anion production. H/R primed both adherent and fluid-phase PMNs for subsequent up-regulation of CD32 and CD16 (Fcgamma receptors) when stimulated with FMLP and primed both Fcgamma and complement (CD35, CD11b/CD18) receptors when stimulated with PMA. Kinetics assays demonstrated maximal up-regulation of CD32 and CD16 induced by H/R plus FMLP after 30 minutes of reoxygenation, whereas maximal receptor stimulation by H/R plus PMA occurred within 15 minutes of reoxygenation. Neither actinomycin D nor cycloheximide abrogated the effect of H/R with subsequent stimulation of PMNs on receptor expression; however, 10(-5) to 10(-8) mol/L concentrations of either taxol or phalloidin completely abrogated the effect of H/R plus FMLP or PMA on opsonic receptor expression. The effect of H/R plus FMLP on CD32 and CD16 expression was blocked by pertussis toxin, whereas staurosporine, H-7, H-9, and genistein had no effect. Conversely, the effect of H/R plus PMA on CD32, CD16, CD35, and CD11b/CD18 expression was blocked by staurosporine and H-7 but not by H-9, pertussis toxin, or genistein. The up-regulation of CD32, CD16, CD35, and CD11b/CD18 induced by H/R plus FMLP or PMA in the presence or absence of matrix proteins resulted in the increased rosetting of E-anti-CD32, E anti-CD16, E-Con A, EC3b, and EC3bi, respectively. Reduced nicotinamide adenine dinucleotide phosphate oxidase inhibition with diphenyleneiodonium blocked the effect of H/R on receptor expression, degranulation, and superoxide anion production. These results demonstrate that H/R primes PMNs for subsequent receptor up-regulation by divergent intracellular signal transduction pathways and that the receptors induced to the cell surface are biologically active.
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PMID:Polymorphonuclear leukocyte opsonic receptor expression after hypoxia/reoxygenation. 865 40


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