Rapid induction of neutrophil-endothelial adhesion by endothelial complement fixation.
The adhesion of neutrophils to vascular endothelium is an early event in their recruitment into acute inflammatory lesions. In evaluating potential neutrophil-endothelial adhesive mechanisms in acute inflammation, important considerations are that adhesion in vivo may occur very rapidly following injury and that the specificity of the reaction resides in altered endothelium. That is, neutrophils adhere only to altered endothelium adjacent to an inflammatory focus, rather than at random as would be expected if activation of neutrophils were the initiator of adhesion. We have explored a possible bridging role for complement in causing early neutrophil-endothelial cell adhesion. The complement system is involved in inflammatory processes, is capable of rapid amplification, and endothelial complement fixation at sites of inflammation could generate an endothelium-restricted signal for neutrophil adhesion. We have now developed a model in which this can be investigated without complicating factors such as immunoglobulin deposition, by constructing a novel molecule, a hybrid of the endothelial binding lectin Ulex europaeus I and of the complement activator cobra venom factor. This molecule has the capacity to cause fixation of complement on human umbilical vein endothelial cells. We show that complement fixation is a potent and rapid stimulus for neutrophil adhesion. Neutrophil adhesion requires only endothelial deposition of C3, and is mediated through the type 3 complement receptor.
Marks
R M
RM
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602.
Todd
R F
RF
Ward
P A
PA
D002448:Cell Adhesion / Q000187:drug effects; D003168:Complement Fixation Tests; D003165:Complement System Proteins / Q000502:physiology*; D004546:Elapid Venoms / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D009504:Neutrophils / Q000502:physiology*
D004546:Elapid Venoms; C016310:cobra venom factor; D003165:Complement System Proteins