EXPRESSION OF RECEPTORS FOR C5A ANAPHYLATOXIN (CD88) ON HUMAN BRONCHIAL EPITHELIAL-CELLS - ENHANCEMENT OF C5A-MEDIATED RELEASE OF IL-8 UPONEXPOSURE TO CIGARETTE-SMOKE

Results are presented that demonstrate a heightened responsiveness of human bronchial epithelial cells (HBECs) toward the complement-derived anaphylatoxin C5a when these cells are exposed to cigarette smoke. Th is C5a response is possible because we show at both the protein and mR NA levels that HBECs constitutively express receptors for C5a (C5aR, C D88), Control (untreated) HBECs responded to C5a (50 nM) by releasing the proinflammatory cytokine IL-8 at low but significant levels. Howev er, exposure of HBECs to 5% cigarette smoke extract (CSE) for at least 15 min resulted in an increase in the ability of an anti-human C5aR A b to bind to the cell surface. CSE-treated HBECs responded in a dose-d ependent fashion to human recombinant C5a and to a conformationally bi ased decapeptide agonist of C5a (YSFKPMPLaR) by releasing IL-8, The le vels of IL-8 released in response to C5a were significantly greater in CSE-treated HBECs than in control HBECs, Moreover, this C5a-mediated release of IL-8 from CSE-treated HBECs was significantly reduced in th e presence of the anti-human;C5aR Ab, These results indicate that HBEC s constitutively express C5aRs and that exposure to environmental irri tants such as cigarette smoke modulates the expression and responsiven ess of these C5aRs toward the C5a-mediated release of IL-8.