Complement-induced granulocyte adhesion and aggregation are mediated by different factors: evidence for non-equivalence of the two cell functions.
Cell-cell aggregation and cell-substratum adherence, two functional manifestations of granulocytes of potential clinical relevance, are widely considered to result from identical cell membrane alterations. Our study casts doubt on this assumption and defines the complement-derived adhesion-inducing (pectic)/enzyme releasing activity as an entity that is clearly separable from the chemotactic/aggregating activity (C5adesArg). Using selective activators of the alternative and the classical pathway of the complement system, unexpected dissimilarities were observed. Adhesion inducing potency that went in parallel with secondary granule content liberation, and respiratory burst activation (hexose monophosphate shunt activation), was confined to alternate pathway activators, was heat-labile (50 degrees) and could be inhibited by the protease inhibitor di-isopropylfluorophosphate. In contrast, plasma activated with aggregated gamma-globulin or cobra venom factor had no pectic/burst activating capacity but was equally potent in inducing heat- and DFP-resistant chemotactic-aggregating activity. It was further shown that, even in the presence of cytochalasin B, C5adesArg (evoked in whole plasma) does not liberate secondary granule constituents. These findings were corroborated by using highly purified C5adesArg. Our data suggest that the complement system plays a dual role in PMN accumulation at the inflammatory focus: whereas C5adesArg orientates cellular movement toward the site of bacterial invasion, the complement-dependent pexin(s) is mainly involved in confining infections localized by the adhesion-induced trapping of highly reactive cells.
D002448:Cell Adhesion; D002449:Cell Aggregation; D002634:Chemotaxis, Leukocyte; D003167:Complement Activation; D003165:Complement System Proteins / Q000502:physiology*; D006358:Hot Temperature; D006801:Humans; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology*
D003165:Complement System Proteins