Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Stimulation of monoblastic U937 cells with transforming growth factor beta 1 and 1,25-(OH)2 vitamin D3 (TGF-beta 1/D3) upregulates urokinase receptor (uPAR) and confers urokinase-dependent adhesiveness to the cells for serum- or vitronectin-coated surfaces. Recent studies show that uPAR itself is a high-affinity adhesion receptor for vitronectin and that urokinase (uPA) is an activator of this adhesive function. In the course of exploring possible G-protein involvement in this adhesion it was observed that TGF-beta 1/D3-primed U937 cells became adhesive to vitronectin in an uPAR-dependent manner when exposed to pertussis toxin (PTX). The adherent response is concentration- and time-dependent, and was not due to the ADP-ribosyltransferase activity of the toxin because the purified B-subunit of PTX was equally effective. Although promoting adhesion to serum- or vitronectin-coated surfaces, PTX blocked spontaneous cell adhesion to fibrinogen, an endogenous ligand for the Mac-1 receptor (CD11b/CD18). Flow cytometry study showed that expression of the alpha-subunit of Mac-1 (CD11b) on primed cells was increased by nearly threefold. Monoclonal antibody to CD11b abolished the PTX-induced cell adhesion and the binding of the primed cells to PTX-coated plates. Activation of Mac-1 receptor by its endogenous ligand fibrinogen induced cell adherent response similar to PTX. PTX, but not uPA, triggered a rapid rise in [Ca2+]i in primed U937 cells, and PTX-induced adhesion was significantly attenuated by 1,2-bis-(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/acetoxy-methyl ester (BAPTA/AM), a selective membrane-permeant [Ca2+]i chelator. PTX-induced cell adhesion was also prevented by antibodies to uPAR and by conditioned medium containing soluble uPAR. Together these data indicate that PTX B-subunit may bind to Mac-1 integrin, which leads to a rapid rise in [Ca2+]i and subsequent activation of uPAR for adherence to vitronectin, suggesting a functional link between Mac-1 and activation of uPAR important to cellular trafficking and host defence in response to Bordetella pertussis infection.
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PMID:Mechanisms of pertussis toxin-induced myelomonocytic cell adhesion: role of Mac-1(CD11b/CD18) and urokinase receptor (CD87). 870 56

The CC chemokines regulated on activation normal T expressed and secreted (RANTES) and monocyte chemotactic protein 3 (MCP-3), and the anaphylatoxin C5a, induce activation, degranulation, chemotaxis, and transendothelial migration of eosinophils. Adhesion assays on purified ligands showed differential regulation of beta 1 and beta 2 integrin avidity in eosinophils. Adhesiveness of VLA-4 (alpha 4 beta 1, CD29/CD49d) for vascular cell adhesion molecule 1 or fibronectin was rapidly increased but subsequently reduced by RANTES, MCP-3, or C5a. The deactivation of VLA-4 lead to cell detachment, whereas phorbol 12-myristate 13-acetate induced sustained activation of VLA-4. In contrast, chemoattractants stimulated a prolonged increase in the adhesiveness of Mac-1 (alpha M beta 2, CD11b/CD18) for intercellular adhesion molecule 1. Inhibition by pertussis toxin confirmed signaling via G protein-coupled receptors. Chemoattractants induced transient, while phorbol 12-myristate 13-acetate induced sustained actin polymerization. Disruption of actin filaments by cytochalasins inhibited increases in avidity of VLA-4 but not of Mac-1. Chemoattractants did not upregulate a Mn2+-inducible beta 1 neoepitope defined by the mAb 9EG7, but induced prolonged expression of a Mac-1 activation epitope recognized by the mAb CBRM1/5. This mAb inhibited chemoattractant-stimulated adhesion of eosinophils to intercellular adhesion molecule 1. Thus, regulation of VLA-4 was dependent on the actin cytoskeleton, whereas conformational changes appeared to be crucial for activation of Mac-1. To our knowledge, this is the first demonstration that physiological agonists, such as chemoattractants, can differentially regulate the avidity of a beta 1 and a beta 2 integrin expressed on the same leukocyte.
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PMID:Differential regulation of beta 1 and beta 2 integrin avidity by chemoattractants in eosinophils. 885 87

Asymptomatic infection due to Bordetella pertussis has been suggested to be one cause of sudden infant death syndrome (SIDS). We examined developmental and environmental factors previously found to affect binding of another toxigenic species, Staphylococcus aureus, to human epithelial cells: expression of the Lewis(a) antigen; infection with respiratory syncytial virus (RSV); exposure to cigarette smoke; and the inhibitory effect of breast milk on bacterial binding. Binding of two strains of B. pertussis (8002 and 250825) to buccal epithelial cells was significantly reduced by treating the cells with monoclonal antibodies to Lewis(a) (P < 0.05) and Lewis(x) (P < 0.01) antigens. Both strains bound in significantly greater numbers to cells from smokers compared with cells from non-smokers (P < 0.05). HEp-2 cells infected with RSV subtypes A or B had higher binding indices for both 8002 (P < 0.001) and 250825 (P < 0.01). On RSV-infected cells, there was significantly enhanced binding of monoclonal antibodies to Lewis(x) (P < 0.05), CD14 (P < 0.001) and CD18 (P < 0.01); and pre-treatment of cells with anti-CD14 or CD18 also significantly reduced binding of both strains of B. pertussis. Pre-treatment of the bacteria with human milk significantly reduced their binding to epithelial cells. The results are discussed in relation to our three-year survey of bacterial carriage among 253 healthy infants, their mothers and local SIDS cases between 1993-1995 and in relation to the change to an earlier immunisation schedule for infants and the recent decline in SIDS in Britain.
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PMID:Developmental and environmental factors that enhance binding of Bordetella pertussis to human epithelial cells in relation to sudden infant death syndrome (SIDS). 895 53

Polymorphonuclear leukocyte-endothelial cell (PMN-EC) adhesion and the O2- production by subsequently triggered polymorphonuclear leukocytes (PMN) must be involved in the development of multiple organ failure at septic inflammatory sites. In this study, the adhesion and O2- production of PMN treated with LPS and serum, were markedly enhanced on the EC monolayer by treatment with TNF-alpha or LPS. However, in the intact EC monolayer, neither adhesion nor O2- production was increased. Monoclonal antibodies (mAb) against CD18, CD11b, and ICAM-1 inhibited PMN-EC adhesion. All antibodies except for anti-CD11b mAb had no effect on O2- production by adhered PMN. Anti-CD11b mAb stimulated O2- production in a PMN cell suspension. The pertussis toxin, an inhibitor of some G-proteins, inhibited this reaction. These findings indicate that the adhesion mediated by CD11b provides the signal for O2- production by PMN. This O2- production may involve a signal transduction mechanism mediated by pertussis toxin-sensitive G-proteins.
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PMID:Regulation of neutrophil O2- production by neutrophil-endothelial cell interaction via CD11b: its modulation by tumor necrosis factor-alpha (TNF-alpha) and lipopolysaccharide (LPS). 899 Jun 25

We previously demonstrated that a mAb to human neutrophils, designated 3H9, which was established by screening for inhibition of neutrophil adherence to plastic plates containing fetal bovine serum, enhanced both n-formyl-methionyl-leucyl-phenylalanine (FMLP)-induced chemotaxis and random migration of neutrophils. In the present study, we examined the mechanisms of 3H9-induced enhancement of neutrophil locomotion in the phagokinetic track assay. 3H9-induced neutrophil locomotion maintained a straight path which was different from the track resulting from FMLP-stimulated locomotion. This 3H9-induced migration required extracellular Ca2+. beta 2-Integrin activation was a prerequisite for the increase in cytosolic free calcium induced by 3H9 treatment. However, stimulation by 3H9 did not induce an increase in F-actin, even after CD18 activation. Signal transduction after molecular recognition by 3H9 was not mediated by pertussis toxin-sensitive, heterotrimeric G proteins. These results suggest that 3H9 enhances neutrophil migration by mechanisms which are different from those involved in usual chemoattractant-induced migration. Neutrophil surface molecules recognized by 3H9 may play a crucial role in the regulation of transendothelial migration of leukocytes.
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PMID:External calcium-dependent, F-actin-independent and pertussis toxin-insensitive novel neutrophil locomotion induced by a mAb. 918 22

Pertussis toxin (PTX) was thought to bind Mac-1 integrin receptor (CD11b/CD18) on TGF-beta1/D3-primed U937 cells and induced cellular adhesion to serum-coated plate. The present study was to investigate the signal transduction pathway utilized by PTX to initiate myeloid cell adhesion in serum. Immunoblotting study showed that PTX induced tyrosine phosphorylation of two cytoplasmic proteins of 150 kDa and 90 kDa in TGF-beta1/D3-primed U937 cells in a time-dependent manner. In addition, PTX-induced myelomonocytic cell adhesion was abolished in the presence of genistein (100 microM), a specific tyrosine kinase inhibitor. 2LPM19c (2 microg/ml), a mouse monoclonal antibody against the CD11b subunit of Mac-1 integrin, or ethylenediamine tetraacetic acid (EDTA, 5 mM) prevented PTX-mediated U937 cell adhesion. On the other hand, nifedipine (1 microM), a calcium channel blocker, significantly reduced PTX-induced U937 cell adhesion. Taken together, it is suggested that binding of PTX to Mac-1 integrin receptor on primed U937 cells triggers protein tyrosine phosphorylation and, to a lesser extent, Ca(+2) influx, which eventually lead to monocytic cell adhesion in serum.
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PMID:Signaling mechanisms of pertussis toxin-induced myelomonocytic cell adhesion: role of tyrosine phosphorylation. 924 Apr 64

We have used the Stamper-Woodruff frozen-section assay (FSA) to characterize the integrin and activation steps involved in adhesion of peripheral blood eosinophils and neutrophils to nasal polyp endothelium (NPE). Eosinophil and neutrophil adhesion was significantly inhibited by monoclonal antibodies (mAbs) against CD18 (beta2) and CD11a-c. Eosinophil adhesion was also inhibited to a lesser extent by mAbs against CD29 (beta1), CD49d (alpha4), and vascular cell adhesion molecule-1. The involvement of integrins raised the possibility of an activation step being involved in the adhesion process. Although stimulation of the cells with granulocyte macrophage colony-stimulating factor (GM-CSF) before the assay failed to modulate adhesion, binding was inhibited by up to 50% by treatment of the leukocytes with azide. In addition, neutrophil adhesion was completely abrogated by pertussis toxin (PT) and inhibited by about 50% by the platelet-activating factor antagonist WEB 2086 and antibodies against interleukin (IL)-8 and the two IL-8 receptors IL8RA and IL8RB (C-X-CR1 and -CR2). In contrast, eosinophil adhesion was unaffected by PT, WEB 2086, or anti-IL8R mAbs. mAbs against CCR-3, IL-3, IL-5, and GM-CSF also had no effect. This study demonstrates that eosinophil and neutrophil adhesion to NPE in the FSA conforms to the multistep paradigm for leukocyte adhesion and can be used to model the molecular basis for adhesion to endothelium in the context of chronic inflammatory disease. Using this assay, we have observed significant differences in integrin usage between eosinophils and neutrophils and a striking difference in the mechanism of integrin activation. These differences could explain, in part, the preferential accumulation of eosinophils in diseases such as asthma.
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PMID:Characterization of the integrin and activation steps mediating human eosinophil and neutrophil adhesion to chronically inflamed airway endothelium. 1034 Sep 44

Human neutrophils, incubated with Cr51-labelled B lymphoblastoid Raji cells in the presence of the anti-target monoclonal antibody (mAb) Lym-1 plus formyl-methionyl-leucyl-phenylalanine (FMLP) or tumour necrosis factor alpha (TNF-alpha), were found to induce significant C51 release, i.e. significant cytolysis. The lytic process was inhibited by mAb IV.3, specific for the Fcgamma receptor (FcgammaR) type II. The mAb 3G8, which reacts with FcgammaR type III, was ineffective. Moreover, the lysis was inhibited by the anti-CD18 mAb MEM-48. These data suggest that FMLP/Lym-1 as well as TNF-alpha/Lym-1 cytolytic systems strictly require FcgammaRII and CD18 integrins. As the lysis induced by TNF-alpha/Lym-1 was prevented by pertussis toxin (PT), PT-sensitive G-proteins are likely to intervene in post-FcgammaRII signal transduction. Both the FMLP- and the TNF-alpha-dependent systems were also found to be equally susceptible to inhibition by various inhibitors of kinases (genistein, staurosporin, 1-(5-isoquinolinnylsulphonyl)-2-methylpiperazine and wortmannin). On the contrary, an inhibitor of protein kinase C (bis-indolyl-maleimide, BIM) was effective only in the FMLP/Lym-1 cytolytic system. Therefore, it appears that signals delivered by FMLP or TNF-alpha, BIM-sensitive and insensitive respectively, converge and synergize with those from G-protein-coupled FcgammaRII and, probably, CD18-integrins to promote the expression of the neutrophil cytolytic potential.
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PMID:FMLP- and TNF-stimulated monoclonal Lym-1 antibody-dependent lysis of B lymphoblastoid tumour targets by neutrophils. 1040 34

Pertussis toxin treatment in macaques inhibits lymphocyte extravasation from the blood and leads to transient lymphocytosis and leukocytosis. We examined lymphocyte adhesion molecules known to be involved in the extravasation process to find possible mechanisms for the effects of pertussis toxin treatment. The two subunits of LFA-1, CD11a and CD18, showed decreased surface expression on lymphocytes from pertussis toxin treated animals compared to untreated animals. The adhesion molecule CD44, and the alpha subunit of the integrin VLA-4 (CD49d) were not decreased by pertussis toxin treatment. Lower surface expression of CD11a and CD18 was observed on all lymphocyte subsets and was correlated inversely with the extent of lymphocytosis. The magnitude of lymphocytosis after pertussis toxin treatment was higher in SIV-infected macaques than in uninfected animals. However, changes in LFA-1 levels were similar in both groups. These data show that LFA-1 surface levels are affected by pertussis toxin in vivo and this change may account in part, for the ability of pertussis toxin to induce lymphocytosis.
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PMID:Pertussis toxin treatment in vivo reduces surface expression of the adhesion integrin leukocyte function antigen-1 (LFA-1). 1062 3

Lipoxins (LX) are lipoxygenase-derived eicosanoids generated during inflammation. LX inhibit polymorphonuclear neutrophil (PMN) chemotaxis and adhesion and are putative braking signals for PMN-mediated tissue injury. In this study, we report that LXA4 promotes another important step in the resolution phase of inflammation, namely, phagocytosis of apoptotic PMN by monocyte-derived macrophages (Mphi). LXA4 triggered rapid, concentration-dependent uptake of apoptotic PMN. This bioactivity was shared by stable synthetic LXA4 analogues (picomolar concentrations) but not by other eicosanoids tested. LXA4-triggered phagocytosis did not provoke IL-8 or monocyte chemoattractant protein-1 release. LXA4-induced phagocytosis was attenuated by anti-CD36, alphavbeta3, and CD18 mAbs. LXA4-triggered PMN uptake was inhibited by pertussis toxin and by 8-bromo-cAMP and was mimicked by Rp-cAMP, a protein kinase A inhibitor. LXA4 attenuated PGE2-stimulated protein kinase A activation in Mphi. These results suggest that LXA4 is an endogenous stimulus for PMN clearance during inflammation and provide a novel rationale for using stable synthetic analogues as anti-inflammatory compounds in vivo.
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PMID:Cutting edge: lipoxins rapidly stimulate nonphlogistic phagocytosis of apoptotic neutrophils by monocyte-derived macrophages. 1065 8


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