CNTFR alpha alone or in combination with CNTF promotes macrophage chemotaxis in vitro.
Microchemotaxis chambers were used to investigate whether one aspect of ciliary neurotrophic factor CNTF's role as a lesion factor might be to promote the initial early recruitment of macrophages, which express the signal transducing receptor components, gp130 and LIFRbeta. CNTFRalpha alone, or in combination with CNTF, elicited concentration-dependent macrophage chemotaxis that was inhibited by a neutralizing gp 130 antibody. IL-6, but not LIF, similarly promoted gp 130-dependent macrophage chemotaxis. Stimulation of macrophages with either CNTFRalpha in combination with CNTF or IL-6 alone resulted in tyrosine phosphorylation of an approximately 130 kD protein, presumed to be gp130. Macrophage chemotaxis induced by the combination of CNTFRalpha and CNTF was inhibited in a dose-dependent fashion by wortmannin, LY294002 or PD98059, suggesting the involvement of the phosphoinositide-3 kinase and mitogen-activated protein kinase signaling proteins. As CNTFRalpha and CNTF are present, or have immediate access to nerves after injury, these data point to the possibility that this soluble receptor alone or in combination with its ligand may promote the initial early recruitment of macrophages in vivo.
Kobayashi
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Department of Pathology, School of Medicine, University of California, San Diego 92093-0612, USA.
Mizisin
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AP
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology; D002630:Chemotactic Factors / Q000494:pharmacology*; D002633:Chemotaxis / Q000187:drug effects*; D002867:Chromones / Q000494:pharmacology; D020934:Ciliary Neurotrophic Factor / Q000494:pharmacology* / Q000502:physiology; D050822:Cytokine Receptor gp130; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000502:physiology; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D021122:Protein Subunits; D020801:Receptor, Ciliary Neurotrophic Factor / Q000187:drug effects / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D000077191:Wortmannin
D000730:Androstadienes; D015703:Antigens, CD; D002630:Chemotactic Factors; D002867:Chromones; D020934:Ciliary Neurotrophic Factor; D050822:Cytokine Receptor gp130; D004791:Enzyme Inhibitors; D005419:Flavonoids; D006131:Growth Inhibitors; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D008562:Membrane Glycoproteins; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D021122:Protein Subunits; D020801:Receptor, Ciliary Neurotrophic Factor; D011994:Recombinant Proteins; D000077191:Wortmannin; C494199:IL6ST protein, human; C494200:Il6st protein, mouse; C507837:LIF protein, human; C507838:Lif protein, mouse; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one