Gt. Furuta et al., Parallel induction of epithelial surface-associated chemokine and proteoglycan by cellular hypoxia: implications for neutrophil activation, J LEUK BIOL, 68(2), 2000, pp. 251-259
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.