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A role for β 2 integrins (CD11/CD18) in the regulation of cytokine gene expression of polymorphonuclear neutrophils during the inflammatory response
Author(s) -
Walzog Barbara,
Weinmann Pamela,
Jeblonski Frank,
ScharffetterKochanek Karin,
Bommert Kurt,
Gaehtgens Peter
Publication year - 1999
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.13.13.1855
Subject(s) - cd18 , integrin , proinflammatory cytokine , cytokine , integrin alpha m , microbiology and biotechnology , biology , cell adhesion , chemistry , inflammation , immunology , receptor , biochemistry , flow cytometry , cell
Growing evidence supports the idea that adhesion via β 2 integrins not only allows cellular targeting, but also induces intracellular signaling, which in turn activates functional responses of adherent cells. This study investigates whether β 2 integrin‐mediated adhesion of human polymorphonuclear neutrophils (PMN) has a functional impact on cytokine production. Aggregation of the β 2 integrin Mac‐1 (CD11b/CD18) by antibody cross‐linking was found to induce substantial de novo synthesis of IL‐8 mRNA as measured by semiquantitative RT‐PCR and Northern blotting technique, respectively. Induction of IL‐8 mRNA was also observed upon adhesion of PMN to immobilized fibrinogen, a functional equivalent of its clotting product fibrin that serves as a native ligand of Mac‐1. Results were confirmed using PMN derived from CD18‐deficient mice, which were unable to produce MIP‐2 mRNA, a homologue of human IL‐8, in the presence of immobilized fibrinogen. In contrast, a substantial increase of MIP‐2 mRNA was observed when wild‐type PMN were incubated on immobilized fibrinogen. In human PMN, ELISA technique showed that the gene activation that required tyrosine kinase activity resulted in a substantial production and secretion of biologically active IL‐8 and IL‐1β. In contrast, no TNF‐α or IL‐6 production was found, revealing that β 2 integrins mediate differential expression of proinflammatory cytokines. The biological relevance of the present findings was confirmed in an in vivo model of acute inflammation. Altogether, the present findings provide evidence for a functional link between clotting and inflammatory responses that may contribute to the recruitment and/or activation of PMN and other cells at sites of lesion.—Walzog, B., Weinmann, P., Jeblonski, F., Scharffetter‐Kochanek, K., Bommert, K., Gaehtgens, P. A role for β 2 integrins (CD11/CD18) in the regulation of cytokine gene expression of polymorphonuclear neutrophils during the inflammatory response. FASEB J . 13, 1855–1865 (1999)