The properties of human C5a anaphylatoxin. The significance of C5a formation during hemodialysis.
Human C5a anaphylatoxin is a potent bioactive molecule that possesses both spasmogenic and leukocyte-related properties. As such, it normally serves as a local mediator of the acute inflammatory response. Additionally, C5a, through its actions of mononuclear phagocytes, may act to bridge the gap in the acute-chronic inflammatory continuum. While these properties are critical to normal host defense mechanisms, it is now apparent that this anaphylatoxin and/or its des-Arg74 derivative, may exert significant systemic effects that are manifest as cardiopulmonary abnormalities and intravascular activation of granulocytes. Knowledge of these properties is critically important for understanding the clinical sequelae exhibited by patients undergoing extracorporeal circulation since we now know that both hemodialysis and cardiopulmonary bypass [28-30] procedures promote intravascular complement activation and C5a formation. Viewed in this context, it seems reasonable to postulate that many of the immediate and delayed responses to extracorporeal circulation might be mediated by C5a formed in the extracorporeal circuit (table IV). For example, it is now recognized that a few particularly susceptible patients display adverse reactions during the initial phases of hemodialysis. The symptoms of this so-called 'first-use syndrome' may range from severe urticaria and angioedema to life-threatening bronchospasm, hypotension, and cardiopulmonary collapse. Some investigators have presented data which suggest that complement-derived products may be causative of these symptoms in some patients [31]. While this hypothesis remains to be confirmed, present evidence clearly demonstrates that C5a alone may produce many of the observed phenomena. In addition to the acute effects produced by C5a, both our own basic studies and the clinical investigations presented by others at this conference suggest that the long-term effects of repeated C5a exposure in the dialyzed patient may be considerable. Thus, there has been a great deal of interest in the role of complement-derived mediators as initiators of leukocyte degranulation and toxic oxygen radical production and an exploration of the significance of these events in the eventual development of chronic pulmonary fibrosis in the dialyzed patient. Similarly, the effects of repeated exposure to IL-1 that has been postulated to occur as a result of C5a triggering of monocytes during dialysis is currently an active area of investigation.(ABSTRACT TRUNCATED AT 400 WORDS)
Chenoweth
D E
DE
Veterans Administration Medical Center, San Diego, Calif.
D000706:Anaphylatoxins / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D003176:Complement C3 / Q000096:biosynthesis; D015926:Complement C3a; D003182:Complement C5 / Q000096:biosynthesis / Q000378:metabolism / Q000493:pharmacokinetics / Q000502:physiology*; D015936:Complement C5a; D006098:Granulocytes / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D010455:Peptides / Q000502:physiology*; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000378:metabolism; D006435:Renal Dialysis
D000706:Anaphylatoxins; D003176:Complement C3; D003182:Complement C5; D010455:Peptides; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; D015926:Complement C3a; D015936:Complement C5a