title: Evidence for the involvement of phosphatidylinositol 4,5-bisphosphate 3-kinase in CD18-mediated adhesion of human neutrophils to fibrinogen.
abstract: The CD18 integrin mediates chemotaxin-induced adhesion of neutrophils to fibrinogen. In neutrophils chemotaxins activate different intracellular pathways, which metabolize phosphatidylinositol 4,5-bisphosphate. To analyse the functional role of phosphatidylinositol 4,5-bisphosphate 3-kinase in the adhesion response, studies with the fungal metabolite wortmannin and the chemically unrelated compound LY 294002 were performed. These compounds inhibited with similar concentration dependency chemotaxin-induced formation of [32P]phosphatidylinositol 3,4,5-trisphosphate and CD18-mediated adhesion of neutrophils to fibrinogen, but did not influence expression of CD18 molecules at the cell surface. These data suggest involvement of phosphatidylinositol 4,5-bisphosphate 3-kinase in chemokine-induced avidity changes of CD18 integrins.
authors.affiliation: Division of Experimental and Clinical Dermatology, University of Freiburg, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Metzner
authors.forename: M
authors.initials: M
authors.lastname: Heger
authors.forename: C
authors.initials: C
authors.lastname: Hofmann
authors.forename: W
authors.initials: W
authors.lastname: Czech
authors.forename: J
authors.initials: J
authors.lastname: Norgauer
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D018821:CD18 Antigens / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D009025:Morpholines / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D010743:Phospholipids / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D018821:CD18 Antigens; D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D010743:Phospholipids; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D005340:Fibrinogen; D017853:Phosphotransferases (Alcohol Group Acceptor); C068961:phosphatidylinositol 4,5-biphosphate kinase; D010741:Phospholipases A; D000077191:Wortmannin