Hepatocyte growth factor is a potent trigger of neutrophil adhesion through rapid activation of lymphocyte function-associated antigen-1

Shinichiro Mine, Yoshiya Tanaka, Makoto Suematu, Megumi Aso, Takeshi Fujisaki, Shinwa Yamada, Sumiya Eto

研究成果: Article査読

37 被引用数 (Scopus)

抄録

Recruitment of neutrophils into tissue occurs in several pathologic processes such as inflammation, atherosclerosis, thrombosis, and ischemia. In inflammation, the adherence of neutrophils to the endothelium depends on neutrophil integrins. Integrin-mediated adhesion is tightly regulated, ie, integrins do not function if neutrophils are not triggered by certain activation stimuli. We investigated the role of hepatocyte growth factor (HGF) in the adhesion of neutrophils to endothelial cells in inflammation. Our results showed that (a) HGF induced not only lymphocyte function- associated antigen-1 (LFA-1)-mediated adhesion of neutrophils to endothelial cells but also transmigration of neutrophils in a concentration-dependent manner; (b) HGF functionally transformed neutrophil integrin LFA-1 to active form and reduced surface L-selectin expression level; (c) HGF induced F- actin polymerization and cytoskeletal rearrangement within seconds; (d) genistein, a tyrosine kinase inhibitor, as well as wortmannin, a phosphoinositide 3 (PI 3)-kinase inhibitor, inhibited both F-actin polymerization and LFA-1-mediated adhesion of neutrophils to endothelial cells; and (e) neutrophils in cutaneous inflamed tissue highly expressed HGF and serum levels of HGF were elevated in patients with Behcet's disease, which is associated with neutrophilic vasculitis and marked neutrophil accumulation. Our results indicate that HGF plays a pivotal role in integrin- mediated adhesion and transmigration of neutrophils to sites of acute inflammation through cytoskeletal rearrangement activated by tyrosine kinase and PI 3-kinase signaling.

本文言語English
ページ(範囲)1395-1404
ページ数10
ジャーナルLaboratory Investigation
78
11
出版ステータスPublished - 1998 11月 1

ASJC Scopus subject areas

  • 病理学および法医学
  • 分子生物学
  • 細胞生物学

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