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Heterologous desensitization of IL‐8‐mediated chemotaxis in human neutrophils by a cell‐binding fragment of fibronectin
Author(s) -
Stanton Kimberly J.,
Frewin Mary Beth,
Gudewicz Paul W.
Publication year - 1999
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 - 10.1002/jlb.65.4.515
Subject(s) - chemotaxis , heterologous , cxc chemokine receptors , biology , fibronectin , microbiology and biotechnology , desensitization (medicine) , phosphorylation , receptor , integrin , chemokine , chemokine receptor , biochemistry , gene , extracellular matrix
In this study, we have explored the mechanism for the desensitization of IL‐8‐mediated neutrophil chemotaxis by a cell‐binding fragment of fibronectin (120‐kDa FN). Preincubation of neutrophil suspensions with the 120‐kDa FN fragment resulted in a heterologous desensitization of IL‐8‐mediated chemotaxis while not affecting neutrophil chemotaxis to either fMLP or zymosan‐activated serum. Preincubation of neutrophils with the βx‐integrin‐activating antibody (TS2/16) mimicked the effects of the 120‐kDa FN fragment while preincubating neutrophils with the β 1 ‐integrin blocking antibody (mAb13) abrogated the inhibitory effects of the 120‐kDa FN fragment on IL‐8‐mediated chemotaxis. Furthermore, we also demonstrated that the 120‐kDa FN fragment did not inhibit chemotaxis to the CXC chemokine MGSA/GROα which interacts with high affinity to the IL‐8 receptor B (CXCR2). By in vivo phosphorylation of neutrophils and probing lysates with an anti‐CXCR1 antibody, we demonstrated that the addition of the cell‐binding fragment of fibronectin resulted in a time‐dependent phosphorylation of CXCR1. These findings suggest that the mechanism of heterologous desensitization of IL‐8‐mediated chemotaxis following ligation of FN‐dependent integrins is the result of phosphorylation of the CXCR1 receptor. J. Leukoc. Biol. 65: 515–522; 1999.