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Parallel induction of epithelial surface‐associated chemokine and proteoglycan by cellular hypoxia: implications for neutrophil activation
Author(s) -
Furuta Glenn T.,
Dzus Andrea L.,
Taylor Cormac T.,
Colgan Sean P.
Publication year - 2000
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.68.2.251
Subject(s) - chemokine , microbiology and biotechnology , interleukin 8 , biology , epithelium , hypoxia (environmental) , perlecan , integrin alpha m , proteoglycan , immunology , inflammation , chemistry , extracellular matrix , immune system , genetics , organic chemistry , oxygen
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 (pO 2 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 β 2 ‐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.