Parallel induction of epithelial surface-associated chemokine and proteoglycan by cellular hypoxia: implications for neutrophil activation

Neutrophil-induced damage to the protective epithelium has been implicated in mucosal disorders associated with hypoxia, and such damage may be initia ted by epithelial-derived chemokines, Because chemokines can hind to membra ne proteoglycans, we hypothesized that chemokines may associate with epithe lial surfaces and activate polymorphonuclear neutrophils (PMN). Epithelial hypoxia (pO(2) 20 torr) resulted in a time-dependent induction of interleuk in-8 (IL-8) mRNA, soluble protein, as well as surface protein. Such surface IL-8 expression was demonstrated to be dependent on heparinase III express ion, and extensions of these experiments indicated that hypoxia induces epi thelial perlecan expression in parallel with IL-8, Finally, co-incubation o f post-hypoxic epithelia with human PMN induced IL-8-dependent expression o f the PMN beta(2)-integrin CD11b/18. These data indicate that chemokines li berated from epithelia may exist in a surface-bound, bioactive form and tha t hypoxia may regulate proteoglycan expression.