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 initiated by epithelial-derived chemokines. Because chemokines can bind to membrane proteoglycans, we hypothesized that chemokines may associate with epithelial surfaces and activate polymorphonuclear neutrophils (PMN). Epithelial hypoxia (pO2 20 torr) resulted in a time-dependent induction of interleukin-8 (IL-8) mRNA, soluble protein, as well as surface protein. Such surface IL-8 expression was demonstrated to be dependent on heparinase III expression, and extensions of these experiments indicated that hypoxia induces epithelial perlecan expression in parallel with IL-8. Finally, co-incubation of post-hypoxic epithelia with human PMN induced IL-8-dependent expression of the PMN beta2-integrin CD11b/18. These data indicate that chemokines liberated from epithelia may exist in a surface-bound, bioactive form and that hypoxia may regulate proteoglycan expression.
Furuta
G T
GT
Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Dzus
A L
AL
Taylor
C T
CT
Colgan
S P
SP
D018821:CD18 Antigens / Q000378:metabolism; D002450:Cell Communication; D015687:Cell Hypoxia; D002460:Cell Line; D018920:Coculture Techniques; D019812:Heparan Sulfate Proteoglycans / Q000096:biosynthesis*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology*; D018375:Neutrophil Activation; D011133:Polysaccharide-Lyases / Q000096:biosynthesis*
D018821:CD18 Antigens; D019812:Heparan Sulfate Proteoglycans; D016209:Interleukin-8; C071927:perlecan; D011133:Polysaccharide-Lyases; C021349:heparitinsulfate lyase