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

Specific binding of Bordetella pertussis and Neisseria meningitidis endotoxins to human monocytes and murine macrophages was demonstrated. Binding of B. pertussis endotoxin could be inhibited by endotoxins of Salmonella minnesota, Escherichia coli, and Klebsiella pneumoniae, the extent of inhibition being dependent on the origin of the lipopolysaccharides and on the origin of the mononuclear phagocytic cells. The binding of B. pertussis and N. meningitidis endotoxins which was mediated by the polysaccharide region of the endotoxins was serum dependent. The results indicated that the binding of endotoxin was promoted neither by natural antibodies directed against the endotoxin nor by proteins known to combine with endotoxins: immunoglobulins, albumin, or fibronectin; we have provided some evidence that complement components may play a role in the specific binding of endotoxins to the monocyte/macrophage membrane.
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PMID:Specific binding of endotoxin to human monocytes and mouse macrophages: serum requirement. 285 97

Although many functions of phagocytes are known to be regulated by guanosine triphosphate (GTP)-binding proteins, phagocytosis itself has not been considered one of these. However, previous studies have examined only unstimulated neutrophil phagocytosis. Motivated by our previous work, which showed that stimulated neutrophil phagocytosis is regulated by GTP-binding proteins (H. D. Gresham, M. G. Peters, and E. J. Brown. 1986. J. Cell Biol. 103:215a), we have examined the effect of pertussis toxin (PT) on monocyte receptor-mediated phagocytosis. PT inhibited unstimulated and fibronectin-stimulated IgG-mediated phagocytosis and also inhibited C3b-mediated phagocytosis stimulated by fibronectin or phorbol dibutyrate. Cholera toxin (CT) had no effect on unstimulated or stimulated phagocytosis mediated by IgG or C3b. PT inhibition of phagocytosis was not mediated via increases in cellular cAMP levels or by inhibition of the respiratory burst. Inhibition of phagocytosis did not result from decreased numbers of plasma membrane opsonin receptors nor decreased ability to bind opsonized targets. Although phorbol ester-stimulated phagocytosis was inhibited by PT, ligand-independent internalization of CR1 stimulated by phorbol dibutyrate proceeded normally in PT-intoxicated cells. We conclude that a PT-sensitive GTP-binding protein does regulate phagocytic function in monocytes. This protein operates on a molecular mechanism specific to the process of ingestion in both unstimulated monocytes and in cells stimulated to increase phagocytosis. Because unstimulated neutrophil phagocytosis is unaffected by PT or CT, and stimulated neutrophil phagocytosis is inhibited by both PT and CT, our data also demonstrate that monocytes and neutrophils have distinct mechanisms for regulation of phagocytic function.
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PMID:Molecular regulation of phagocyte function. Evidence for involvement of a guanosine triphosphate-binding protein in opsonin-mediated phagocytosis by monocytes. 311 17

Leukoclastic vasculitis is thought to be initiated by deposition of immune complexes (ICs) in the vascular wall. To study the neutrophil response in a related in vitro model, we primed human umbilical vein endothelial cell (HUVEC) monolayers with antibodies against human fibronectin. The resulting respiratory burst to the immobilized ICs depended on the antibody concentration used to prime the monolayers and included a marked release of primary and secondary granule constituents. On IC-bearing HUVEC monolayers, but not on ICs directly bound to tissue culture dishes, blocking monoclonal antibodies (mAbs) to crystallizable fragment-gamma receptor II (Fc gamma RII) and Fc gamma RIII markedly inhibited the respiratory burst and the release of elastase. However, on both surfaces the neutrophil response was strongly inhibited by mAbs against CD18. Regardless of whether we used neutrophils from a patient with severe paroxysmal nocturnal hemoglobinuria (PNH) lacking the Fc gamma RIII, or whether the Fc gamma RII-mediated signal transduction was blocked by pertussis toxin, the respiratory burst to the IC-bearing HUVECs was essentially unchanged. With PNH neutrophils, the respiratory burst was predominantly blocked by an anti-Fc gamma RII mAb. In contrast, the response of pertussis toxin treated neutrophils was strongly inhibited by a mAb against Fc gamma RIII. Together these data indicate that the answer of neutrophils to ICs immobilized at the endothelial barrier depends on the cooperative function of both low-affinity Fc gamma Rs.
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PMID:Neutrophil activation in response to immune complex-bearing endothelial cells depends on the functional cooperation of Fc gamma RII (CD32) and Fc gamma RIII (CD16). 749 May 18

Nonopsonized Bordetella pertussis bind to human monocytes by means of the virulence factors filamentous hemagglutinin (FHA), pertactin, and the minor fimbrial subunit FimD. Receptors on monocytes that mediate binding of B. pertussis to these cells include complement receptor type 3 (CR3), which binds to FHA of B. pertussis, and very late antigen-5 (VLA-5), which binds to an, as yet, unknown ligand on these bacteria. In the present study, the possibility that FimD acts as a ligand for VLA-5 was investigated. Soluble fibronectin, which is the natural ligand for VLA-5, or mAbs against VLA-5 inhibited binding to monocytes of B. pertussis strains that express FimD but not of mutant strains that lack FimD. Beads that were coated with the fusion protein maltose-binding protein-FimD bound to adherent monocytes, and this binding was inhibited by soluble fibronectin or mAb against the alpha- or beta-chain of VLA-5, while soluble collagen or mAb against VLA-4, VLA-6, CR3, or HLA class II had no effect. Down-modulation of VLA-5 on the apical surface of monocytes by plating the cells onto surfaces precoated with anti-VLA-5 mAb also inhibited binding of beads coated with maltose-binding protein-FimD to monocytes, while precoating of the surfaces with mAb against VLA-6 or CR3 had no effect. These results indicate that VLA-5 on monocytes serves as a receptor for FimD on B. pertussis. Binding of C3bi-coated erythrocytes to monocytes, which is a measure of the binding activity of CR3, was enhanced when monocytes were adhered onto plates precoated with purified fimbriae of B. pertussis, while precoating with fimbriae lacking FimD had no effect. Precoating of the plates with FimD-containing fimbriae also enhanced binding of B. pertussis, which express FHA, but not of strains that lack FHA, to monocytes. The enhanced binding of C3bi-coated erythrocytes and B. pertussis to monocytes could be markedly inhibited by tyrphostin-47, a protein tyrosine kinase inhibitor. These results demonstrate that interaction of FimD of B. pertussis with VLA-5 on monocytes activates CR3, which requires protein tyrosine kinases and results in enhanced binding of B. pertussis to the latter receptor via FHA.
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PMID:Binding of FimD on Bordetella pertussis to very late antigen-5 on monocytes activates complement receptor type 3 via protein tyrosine kinases. 756 Nov 5

Protein kinase C (PKC) isoenzymes are essential components of cell signaling. In this study, we investigated the regulation of PKC-alpha in murine B16 amelanotic melanoma (B16a) cells by the monohydroxy fatty acids 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE] and 13(S)-hydroxyoctadecadienoic acid [13(S)-HODE]. 12(S)-HETE induced a translocation of PKC-alpha to the plasma membrane and focal adhesion plaques, leading to enhanced adhesion of B16a cells to the matrix protein fibronectin. However, 13(S)-HODE inhibited these 12(S)-HETE effects on PKC-alpha. A receptor-mediated mechanism of action for 12(S)-HETE and 13(S)-HODE is supported by the following findings. First, 12(S)-HETE triggered a rapid increase in cellular levels of diacylglycerol and inositol trisphosphate in B16a cells. 13(S)-HODE blocked the 12(S)-HETE-induced bursts of both second messengers. Second, the 12(S)-HETE-increased adhesion of B16a cells to fibronectin was sensitive to inhibition by a phospholipase C inhibitor and pertussis toxin. Finally, a high-affinity binding site (Kd = 1 nM) for 12(S)-HETE was detected in B16a cells, and binding of 12(S)-HETE to B16a cells was effectively inhibited by 13(S)-HODE (IC50 = 4 nM). In summary, our data provide evidence that regulation of PKC-alpha by 12(S)-HETE and 13(S)-HODE may be through a guanine nucleotide-binding protein-linked receptor-mediated hydrolysis of inositol phospholipids.
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PMID:12(S)-hydroxyeicosatetraenoic acid and 13(S)-hydroxyoctadecadienoic acid regulation of protein kinase C-alpha in melanoma cells: role of receptor-mediated hydrolysis of inositol phospholipids. 756 26

Expression of the OmpU outer membrane protein of Vibrio cholerae is positively regulated by toxR, which also regulates critical virulence factors such as cholera toxin and the toxin-coregulated pilus colonization factor. In this study, we have characterized the 38-kDa OmpU protein and investigated its role in the adhesion of V. cholerae to mammalian cells. The amino-terminal sequence of OmpU has similarity with the sequences of Haemophilus influenzae HMW1 and HMW2 adhesins, which, in turn, also have similarity with the sequence of Bordetella pertussis filamentous hemagglutinin. A monoclonal antibody directed against FHA recognized both V. cholerae OmpU and Escherichia coli OmpA, and polyclonal anti-OmpU antibodies recognized FHA and E. coli OmpA, suggesting the existence of common epitopes among these proteins. OmpU was strongly recognized by convalescent-phase serum from volunteers experimentally infected with virulent V. cholerae strains, indicating that OmpU is immunogenic and produced in vivo. OmpU selectively bound to fibronectin and to an arginine-glycine-asparagine (RGD) tripeptide but not to other matrix glycoproteins tested such as collagen or laminin. Antibodies directed against OmpU or their F(ab)2 fragments completely inhibited adhesion of several V. cholerae strains to HeLa, HEp-2, Caco-2, and Henle 407 epithelial cells and also inhibited intestinal colonization and conferred protection in newborn mice against both biotypes (El Tor and classical) of V. cholerae O1. Collectively, these data indicate that OmpU has adhesive properties which may play a role in the pathogenesis of cholera.
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PMID:The OmpU outer membrane protein, a potential adherence factor of Vibrio cholerae. 759 Oct 82

The present study was aimed at defining the chemotactic activity of phosphatidic acid, which is rapidly produced by phagocytes in response to chemotactic agonists. Exogenously added phosphatidic acid induced human monocyte directional migration across polycarbonate filters with an efficacy (number of cell migrated) comparable to that of "classical" chemotactic factors. In lipid specificity studies, activity of phosphatidic acid decreased with increasing acyl chain length but was restored by introducing unsaturation in the acyl chain with the most active form being the natural occurring 18:0,20:4-phosphatidic acid. Lysophosphatidic acid was also active in inducing monocyte migration. No other phospholipid and lysophospholipid tested was effective in this response. Monocyte migration was regulated by a gradient of phosphatidic acid and lysophosphatidic acid bound to the polycarbonate filter, in the absence of detectable soluble chemoattractant. Migration was also observed if phospholipids were bound to fibronectin-coated polycarbonate filters. Thus, phosphatidic acid and lysophosphatidic acid, similarly to other physiological chemoattractants (e.g. C5a and interleukin-8), induce cell migration by an haptotactic mechanism. Phosphatidic acid caused a rapid increase of filamentous actin and, at higher concentrations, induced a rise of intracellular calcium concentration. Monocyte migration to phosphatidic acid and lysophosphatidic acid, but not to diacylglycerol, was inhibited in a concentration-dependent manner by Bordetella pertussis toxin, while cholera toxin was ineffective. In the chemotactic assay, phosphatidic acid and lysophosphatidic acid induced a complete homologous desensitization and only partially cross-desensitized one with each other, or with diacyl-glycerol and monocyte chemotactic protein-1. Suramine inhibited monocyte chemotaxis with a different efficiency phosphatidic acid > lysophosphatidic acid" diacyl-glycerol On the contrary, monocyte chemotactic protein-1-induced chemotaxis was not affected by the drug. Collectively, these data show that phosphatidic acid induces haptotactic migration of monocytes that is at least in part receptor-mediated. These results support a role for phosphatidic acid and lysophosphatidic acid in the regulation of leukocyte accumulation into tissues.
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PMID:Phosphatidic acid and lysophosphatidic acid induce haptotactic migration of human monocytes. 759 25

Leukocyte recruitment is a key step in the inflammatory reaction. Several changes in the cell morphology take place during lymphocyte activation and migration: spheric-shaped resting T cells become polarized during activation, developing a well defined cytoplasmic projection designated as cellular uropod. We found that the chemotactic and proinflammatory chemokines RANTES, MCP-1, and, to a lower extent, MIP-1 alpha, MIP-1 beta, and IL-8, were able to induce uropod formation and ICAM-3 redistribution in T lymphoblasts adhered to ICAM-1 or VCAM-1. A similar chemokine-mediated effect was observed during T cells binding to the fibronectin fragments of 38- and 80-kD, that contain the binding sites for the integrins VLA-4 and VLA-5, respectively. The uropod structure concentrated the ICAM-3 adhesion molecule (a ligand for LFA-1), and emerged to the outer milieu from the area of contact between lymphocyte and protein ligands. In addition, we found that other adhesion molecules such as ICAM-1, CD43, and CD44, also redistributed to the lymphocyte uropod upon RANTES stimulation, whereas a wide number of other cell surface receptors did not redistribute. Chemokines displayed a selective effect among different T cell subsets; MIP-1 beta had more potent action on CD8+ T cells and tumor infiltrating lymphocytes (TIL), whereas RANTES and MIP-1 alpha targeted selectively CD4+ T cells. We have also examined the involvement of cAMP signaling pathway in uropod formation. Interestingly, several cAMP agonists were able to induce uropod formation and ICAM-3 redistribution, whereas H-89, a specific inhibitor of the cAMP-dependent protein kinase, abrogated the chemokine-mediated uropod formation, thus pointing out a role for cAMP-dependent signaling in the development of this cytoplasmic projection. Since the lymphocyte uropod induced by chemokines was completely abrogated by Bordetella pertussis toxin, the formation of this membrane projection appears to be dependent on G proteins signaling pathways. In addition, the involvement of myosin-based cytoskeleton in uropod formation and ICAM-3 redistribution in response to chemokines was suggested by the prevention of this phenomenon with the myosin-disrupting agent butanedione monoxime. Interestingly, this agent also inhibited the ICAM-3-mediated cell aggregation, but not the cell adhesion to substrata. Altogether, these results demonstrate that uropod formation and adhesion receptor redistribution is a novel function mediated by chemokines; this phenomenon may represent a mechanism that significantly contributes to the recruitment of circulating leukocytes to inflammatory foci.
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PMID:Chemokines regulate cellular polarization and adhesion receptor redistribution during lymphocyte interaction with endothelium and extracellular matrix. Involvement of cAMP signaling pathway. 759 74

We have investigated the role of alpha 4 beta 1 and alpha 5 beta 1 integrins in adhesion and migration of T lymphocytes to extracellular matrix proteins. Fibronectin, collagen type IV, and laminin promoted haptotactic and chemotactic migration of lymphoid T cell lines and 12-O-tetradecanoylphorbol 13-acetate-stimulated blood lymphocytes, as determined using a modified Boyden chamber system. Adhesion studies of the T cell lines indicated involvement of both alpha 4 beta 1 and alpha 5 beta 1 integrins in the binding to fibronectin. In contrast, migration assays demonstrated that haptotactic and chemotactic migration to fibronectin in most cases was mediated by only one of the beta 1 integrins. FACS analysis demonstrated comparable amounts of alpha 4 beta 1 and alpha 5 beta 1 on the various cell lines, indicating that utilization of the integrins for migration is not determined by their expression on the cells. Haptotactic migration toward a 120-kDa fibronectin fragment containing the RGD sequence, confirmed the selectivity of the different beta 1 integrins in directing migration. Thus, T cells using alpha 5 beta 1 for haptotaxis against fibronectin were migrating against the 120 kDa fragment whereas T cells using alpha 4 beta 1 were not. These results indicate that the response of T cells to haptotactic and chemotactic signals usually is mediated selectively via alpha 4 beta 1 or alpha 5 beta 1 although binding of fibronectin to the cells is not restricted to only one of the integrins. Cholera toxin and 8-Br-cAMP but not pertussis toxin inhibited migration of T cell lines to fibronectin. Adhesion of these cells to fibronectin was not influenced by any of the toxins. Thus, both in their integrin utilization and in their signaling pathways, adhesion and migration show substantial differences in T cells.
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PMID:Functional specialization of fibronectin-binding beta 1-integrins in T lymphocyte migration. 802 66

Previous studies have shown that fibronectin (Fn) enhances phagocytosis and killing of antibody-coated bacteria by neutrophils and macrophages. In an attempt to understand the mechanism of this enhancement, we have investigated the effects of Fn on phagocytosis-related actin organization as well as respiratory burst activity in neutrophils, monocytes and culture-derived macrophages. Employing an NBD-phallacidin flow cytometric analysis of filamentous actin formation, we found that Fn promotes rapid actin polymerization within 30 seconds in neutrophils, monocytes, and macrophages, but not lymphocytes. Enhancement of actin polymerization by Fn was concentration-dependent and mediated by a pertussis toxin- but not cholera toxin-sensitive G protein. Inhibition of protein kinase C by sphingosine (20 microM), calcium influx by verapamil (0.1 mM), or intracellular calcium mobilization by 8-(N,N-diethyl-amino) octyl-3,4,5-trimethoxybenzoate HCl (TMB-8; 0.1 mM) did not block Fn-enhanced actin polymerization in phagocytes. Incubation of neutrophils and macrophages on microtiter plates precoated with Fn suppressed superoxide (O2-) production induced by IgG- and IgA- opsonized group B streptococci. In contrast, Fn significantly enhanced IgA- and IgG-mediated O2- production by freshly isolated monocytes. These data suggest that Fn enhances phagocytosis, presumably through G protein-coupled cytoskeleton reorganization and augments O2- production by circulating monocytes. In contrast, it appears to suppress O2- production by the active phagocytic cells, neutrophils and macrophages. This may result in enhanced phagocytosis and intracellular killing of microorganisms without damaging interstitial tissues.
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PMID:Effects of fibronectin on actin organization and respiratory burst activity in neutrophils, monocytes, and macrophages. 810 71


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