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)

Incubation of the human glioma cell line HS 683 in the presence of IFN-gamma or retinoic acid strongly stimulates the cell-surface expression of the intercellular adhesion molecule ICAM-1. We have investigated the role of the cAMP-mediated signal transduction pathway in this process and report that pharmacological agents which increased the intracellular levels of cAMP exhibited a biphasic action on ICAM-1 expression in human glioma cell line HS 683. Treatment for 1 hr with 25 microM forskolin or 1 mM isobutylmethylxanthine, or for 12 hr with 100 ng/ml pertussis toxin or 50 micrograms/ml cholera toxin transiently stimulated ICAM-1 expression with a maximal level of expression 8 hr post treatment, after which time ICAM-1 expression returned to the basal level. On the other hand, such pretreatments inhibited the inducing effects of either retinoic acid or IFN-gamma. Indeed, 24 hr after treatment with cAMP-elevating agents, both the retinoic-acid- and the IFN-gamma-induced ICAM-1 expression were inhibited by 60 to 80%, with a maximal 90 to 100% inhibition 72 hr post treatment. This inhibition of the cell-surface expression of ICAM-1 was confirmed at the mRNA level. The intracytoplasmic levels of cAMP were also quantified following treatments with forskolin, retinoic acid or IFN-gamma. In response to forskolin, cAMP levels increased 30-fold within 5 min, whereas a 10-fold increase occurred 60 min following treatment with 10 microM retinoic acid. Interferon gamma, in contrast, did not induce cAMP accumulation. These results were also correlated with an in vitro activation of adenylyl cyclase activity by retinoic acid and inhibition of this activity by IFN-gamma, in a dose-dependent and a GTP-dependent manner. Our results suggest that the suppression of IFN-gamma-induced ICAM-1 expression, obtained upon pre-treatment with cAMP-elevating agents, is due to direct antagonism with IFN-gamma action on adenylyl cyclase. However, the inhibition of retinoic-acid-induced ICAM-1 expression cannot be explained by the same mechanisms. The timing of adenylyl cyclase stimulation and cAMP accumulation, as well as the levels of cAMP accumulation, are probably involved in this inhibition. Our results also emphasize the fact that the induction of ICAM-1 expression is a multi-step process implicating different transductional signals among which cAMP might be involved as a second messenger.
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PMID:Biphasic effect of cAMP-elevating agents on ICAM-1 expression stimulated by retinoic acid and interferon gamma. 137 Apr 36

Antibodies to surface Ig or to the B cell marker CD20 trigger resting human B cells in similar yet distinct ways. Either antibody induces five-fold increases in the expression of the protooncogene, c-myc, as detected with semi-quantitative Northern blot assays. The induction of c-myc mRNA by anti-IgM or anti-CD20 is blocked by inhibitors of protein kinase C (PKC) such as staurosporine and by pretreatment of B cells with phorbol esters to reduce cellular PKC levels. This suggests that PKC is involved in the pathways stimulated by both anti-IgM and anti-CD20. However, anti-CD20, unlike anti-IgM, does not activate significant increases in inositol triphosphate or intracellular-free calcium. Further, anti-CD20-triggered elevation of c-myc mRNA is inhibited by pertussis and cholera toxins, whereas the pathway initiated by anti-IgM if anything is stimulated by pertussis toxin and unchanged by cholera toxin. Further differences in the nature of these two signals were seen when the expression of adhesion/recognition molecules were examined. Anti-IgM consistently induces increased expression of the adhesion molecules CD54 (I-CAM-1) and B7/BB-1 on B cells, but anti-CD20 does not. Yet both anti-CD20 and anti-IgM increase class II MHC, CD18 (LFA-1 beta-chain) and LFA-3 levels. These data suggest that the way in which B cells are activated may influence their surface phenotype and possibly subsequent migration or cell-cell interactions.
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PMID:Activation of dense human tonsilar B cells. Induction of c-myc gene expression via two distinct signal transduction pathways. 170 81

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 recently shown that interferon-gamma (IFN-gamma) stimulated immunocytochemical staining of the intercellular adhesion molecule ICAM-1 may be dependent on inositol phosphate formation in the human renal carcinoma cell line CaKi-1. In the present study we investigated the possible role of GTP-binding proteins (G-proteins) during IFN-gamma signalling. Preincubation of CaKi-1 cells for 24 h with increasing amounts of pertussis toxin (PT) or cholera toxin (CT), two regulators of G-protein activity, inhibited IFN-gamma induced ICAM-1 staining. Preincubation with PT or CT for 24 h also inhibited IFN-gamma induced inositol 1-monophosphate (Ins 1-P), inositol 1,4 bisphosphate (Ins 1,4-P2) and inositol 1,4,5 trisphosphate (Ins 1,4,5-P3) formation. Our findings suggest that IFN-gamma induced ICAM-1 staining and inositol phosphate formation in CaKi-1 cells is dependent on a PT and CT sensitive signalling pathway. This may reflect a role for G-proteins in the coupling of IFN-gamma receptor activation and phospholipase C catalyzed phosphoinositide hydrolysis.
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PMID:Effects of pertussis and cholera toxin on the interferon-gamma stimulated immunocytochemical staining of ICAM-1 and inositol phosphate formation in a human renal carcinoma cell line. 790 88

Pertussis toxin (PT) inhibits invasiveness of T-cell hybridomas in vitro and metastasis formation in vivo. We present evidence for the hypothesis that PT interferes with functional activation of LFA-1. Invasion by TAM2D2 T-cell hybridoma cells of fibroblast monolayers was completely blocked by PT pretreatment, but the cells regained invasiveness in the presence of Mn2+, which activates LFA-1. This invasion was blocked by anti-LFA-1 mAb, and Mn2+ did not stimulate invasiveness of LFA-1-deficient TAM2D2 mutants. TAM2D2 cells did not adhere to surfaces coated with the LFA-1 counterstructure ICAM-1, but Mn2+ induced adhesion. Hence, LFA-1 on TAM2D2 cells requires activation before it can participate in the invasion process. The hypothesis is further supported by the slightly different results obtained with the TAM8C4 T-cell hybridoma. PT inhibited invasion strongly but not completely. This reduced invasion was increased by Mn2+. TAM8C4 cells did adhere to ICAM-1, but Mn2+ enhanced adhesion. Thus, part of LFA-1 on TAM8C4 cells is constitutively active, allowing for some PT-insensitive invasion, but further activation is required for optimal adhesion and invasion. PT blocks G-protein-mediated signals, suggesting that an extracellular factor is involved. This is not a serum component or an autocrine motility factor, since the PT effect was serum-independent, and PT did not inhibit motility. Therefore, it is probably produced by the fibroblasts, and either secreted or associated with the cell surface. These results are in line with the hypothesis that a fibroblast constituent activates LFA-1 via a PT-sensitive G-protein and thus stimulates invasion of T-cell hybridomas into the fibroblast monolayer.
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PMID:Pertussis toxin inhibition of T-cell hybridoma invasion is reversed by manganese-induced activation of LFA-1. 791 6

Experimental autoimmune anterior uveitis (EAAU), a model of uveitis induced by sensitization to melanin associated antigen (MAA) derived from the iris and ciliary body, closely resembles human acute anterior uveitis. The immunopathogenesis of EAAU was studied by immunohistochemical detection of immune cells and the expression of Ia, ICAM-1 and LFA-1 antigens. Male Lewis rats were immunized with bovine MAA, mixed with CFA and pertussis toxin in the hind foot pad. Animals were examined daily by slit-lamp biomicroscopy and serially sacrificed up to 30 days. Immunohistology of the enucleated eyes was performed with monoclonal antibodies W3/25 (CD4), OX-8 (CD8), ED2 (macrophage), OX-33 (B cell), OX-6 (Ia), IA29 (ICAM-1) and WT.1 (LFA-1). During each stage of EAAU, CD4+ T cells predominated over both CD8+ T cells and macrophages in the uvea. Very few B cells were detected during each stage of EAAU. EAAU could not be induced by the adoptive transfer of sera obtained from immunized animals. Low levels of constitutive ICAM-1 and Ia were observed. An increase in ICAM-1 expression was first noted on the epithelial cells of the uveal tract and RPE on day 9 post immunization and preceded LFA-1 and Ia upregulation by approximately 2 days. The immunopathogenesis of EAAU appears to be linked to the presence of the CD4+ T cells.
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PMID:Immunohistochemical studies on melanin associated antigen (MAA) induced experimental autoimmune anterior uveitis (EAAU). 852 6

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

The chemokine RANTES is a potent chemoattractant and activator of T lymphocytes. Mechanisms underlying the RANTES-induced activation of T lymphocytes leading to adhesion and migration have not been fully analyzed. We investigate here the function of RANTES in the regulation of T cell adhesion, specifically the induction of homotypic aggregation. RANTES induced the expression of many important cell surface adhesion and activation receptors in a normal human T cell clone and peripheral blood T lymphocytes, including members of the beta 1 and beta 2 integrin family, CD44, CD50, and CD28. Up-regulation of these markers correlated with RANTES-stimulated homotypic adhesion of T cells. This homotypic aggregation event was RANTES dose-dependent, prolonged, and pertussis toxin-independent, but herbimycin A-sensitive, suggesting that it involves signaling through alternative (G alpha i protein-independent) pathways. Using specific monoclonal antibodies, the homotypic aggregation event was shown to be lymphocyte function-associated antigen-1 (LFA-1)-dependent, with no observable interaction through alpha 4 or beta 1 integrins. Intercellular adhesion molecule-3 (ICAM-3) and possibly ICAM-1 participate as LFA-1 ligands. Additionally, RANTES phosphorylated the beta chain of LFA-1 1-2 min following stimulation. These results imply a specific role for the chemokine RANTES in T cell activation and intercellular adhesion.
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PMID:RANTES stimulation of T lymphocyte adhesion and activation: role for LFA-1 and ICAM-3. 917 93

The homing of lymphocytes to secondary lymphoid organs is thought to involve the action of chemokines. Secondary lymphoid-tissue chemokine (SLC), a high endothelial venule (HEV)-associated chemokine, has emerged as a candidate for participating in this process. We now show that immobilized SLC strongly induces beta2 integrin-mediated binding of T lymphocytes of naive phenotype and B lymphocytes to ICAM-1 under static conditions. This effect is not mediated by beta2 integrin affinity modulation, because SLC does not elicit a beta2 integrin activation epitope (mAb24) on naive T lymphocytes. In a parallel plate flow chamber, lymphocytes rolling via L-selectin are rapidly arrested through beta2 integrins in a pertussis toxin-sensitive manner on a substrate consisting of L-selectin ligands (peripheral lymph node addressins) together with ICAM-1 and SLC. Naive T lymphocytes are arrested on the HEV substrate with sixfold higher efficiency than memory cells. Neutrophils roll, but are not arrested by SLC, whereas they respond to immobilized IL-8 with rapid arrest. Thus, our artificial HEV system recapitulates critical features of lymphocyte interactions with HEV in vivo. These observations strongly point to the participation of SLC in homing of lymphocytes to secondary lymphoid organs.
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PMID:A high endothelial cell-derived chemokine induces rapid, efficient, and subset-selective arrest of rolling T lymphocytes on a reconstituted endothelial substrate. 983 23

The adhesive function of integrins is regulated through cytoplasmic signaling. The present study was performed to investigate the relevance of cytoplasmic signaling and cytoskeletal assembly to integrin-mediated adhesion induced by chemokines. Adhesion of T cells induced by chemokines macrophage inflammatory protein (MIP)-1alpha and MIP-1beta was inhibited by pertussis toxin, wortmannin, and cytochalasin B, suggesting that both G protein-sensitive phosphatidylinositol (PI) 3-kinase activation and cytoskeletal assemblies are involved. The chemokine-induced T cell adhesion could be mimicked by expression of small G proteins, fully activated H-RasV12, or H-RasV12Y40C mutant, which selectively binds to PI 3-kinase, in T cells, inducing activated form of LFA-1alpha and LFA-1-dependent adhesion to ICAM-1. H-Ras expression also induced F-actin polymerization which colocalized with profilin in T cells. Adult T cell leukemia (ATL) cells spontaneously adhered to ICAM-1, which depended on endogenous MIP-1alpha and MIP-1beta through activation of G protein-sensitive PI 3-kinase. H-Ras signal pathway, leading to PI 3-kinase activation, also induced active configuration of LFA-1 and LFA-1-mediated adhesion of ATL cells, whereas expression of a dominant-negative H-Ras mutant failed to do. Profilin-dependent spontaneous polymerization of F-actin in ATL cells was reduced by PI 3-kinase inhibitors. In this paper we propose that H-Ras-mediated activation of PI 3-kinase can be involved in induction of LFA-1-dependent adhesion of T cells, which is relevant to chemokine-mediated signaling, and that profilin may form an important link between chemokine- and/or H-Ras-mediated signals and F-actin polymerization, which results in triggering of LFA-1 on T cells or leukemic T cells.
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PMID:H-Ras signals to cytoskeletal machinery in induction of integrin-mediated adhesion of T cells. 1057 Mar 13


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