title: C1q-bearing immune complexes induce IL-8 secretion in human umbilical vein endothelial cells (HUVEC) through protein tyrosine kinase- and mitogen-activated protein kinase-dependent mechanisms: evidence that the 126 kD phagocytic C1q receptor mediates immune complex activation of HUVEC.
abstract: Endothelial cells play a pivotal role in the initiation and perpetuation of inflammation. C1q, the first component of the classical pathway of complement, is a potent stimulus leading to endothelial cell activation and cytokine production. The specific cellular mechanisms through which endothelial cells are stimulated by C1q are not known. We stimulated human umbilical vein endothelial cells (HUVEC) with either monomeric C1q or C1q-bearing immune complexes (C1q-IC) in the presence or absence of inhibitors of protein tyrosine kinases (PTK) or mitogen-activated protein kinases (MAPK). C1q-IC, but not monomeric C1q, induced IL-8 production in dose- and time-dependent fashion. R3, a cross-linking monoclonal IgM antibody against the 126 kD phagocytic C1q receptor (C1qR), also stimulated IL-8 production. IL-8 mRNA accumulation was detected by Northern blot analysis within 2 h of stimulation by the immune complexes and was enhanced by the addition of cycloheximide. Secretion of IL-8 by C1q-IC stimulated HUVEC was completely blocked by the PTK inhibitor, genistein or the MAPK inhibitor, UO126. These experiments demonstrate that C1q-IC-induced production of IL-8 in HUVEC is dependent upon the activation of PTK and MAPK. These findings also support a role for the phagocytic C1qR as an important activator of HUVEC by immune complexes.
authors.affiliation: Department of Pedatrics, Rheumatology Research, University of Oklahoma Health Sciences Center and the Children's Hospital of Oklahoma, Oklahoma City, 73104, USA.
authors.forename: S
authors.initials: S
authors.lastname: Xiao
authors.forename: C
authors.initials: C
authors.lastname: Xu
authors.forename: J N
authors.initials: JN
authors.lastname: Jarvis
mesh_terms: D000936:Antigen-Antibody Complex / Q000276:immunology*; D002070:Butadienes / Q000494:pharmacology; D002352:Carrier Proteins; D015922:Complement C1q / Q000276:immunology*; D003171:Complement Pathway, Classical; D004730:Endothelium, Vascular / Q000276:immunology*; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D018960:Hyaluronan Receptors; D016209:Interleukin-8 / Q000378:metabolism*; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D010587:Phagocytosis; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011951:Receptors, Complement / Q000378:metabolism; D015398:Signal Transduction; D014471:Umbilical Veins
chemical_list: D000936:Antigen-Antibody Complex; D002070:Butadienes; C087299:C1QBP protein, human; D002352:Carrier Proteins; D018960:Hyaluronan Receptors; D016209:Interleukin-8; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D009570:Nitriles; D011951:Receptors, Complement; C113580:U 0126; C032402:complement 1q receptor; D015922:Complement C1q; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D020928:Mitogen-Activated Protein Kinases