Leukocyte integrin Mac-1 recruits toll/interleukin-1 receptor superfamily signaling intermediates to modulate NF-kappa B activity

Citation
C. Shi et al., Leukocyte integrin Mac-1 recruits toll/interleukin-1 receptor superfamily signaling intermediates to modulate NF-kappa B activity, CIRCUL RES, 89(10), 2001, pp. 859-865
Citations number
43
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
CIRCULATION RESEARCH
ISSN journal
0009-7330 → ACNP
Volume
89
Issue
10
Year of publication
2001
Pages
859 - 865
Database
ISI
SICI code
0009-7330(20011109)89:10<859:LIMRTR>2.0.ZU;2-T
Abstract
The leukocyte integrin Mac-1 (alphaM beta2, CD11b/CD18) regulates important cell functions in inflammation, including adhesion, phagocytosis, and oxid ative burst. Deficiency of Mac-1 reduces vessel wall inflammation and neoin timal thickening after murine carotid artery injury. Although Mac-1 has bee n implicated in modulating AP-1 and NF-kappaB activity, the signal transduc tion pathways involved are undefined. cDNA array analysis of Mac-1-clustere d compared with -nonclustered monocytic THP-1 cells showed increased expres sion of the signal transducer TRAF6 (TNF receptor-associated factor 6), lea ding us to consider the possibility that Mac-1 used a Toll/IL-1 receptor fa mily-like signaling pathway. Mac-1-dependent activation of NF-kappaB was po tentiated by wild-type, and attenuated by dominant negative, TRAF6- and TGF -beta -activated kinase (TAK1) constructs. IRAK1 (IL-1 receptor associated kinase), a kinase immediately upstream of TRAF6, coimmunoprecipitated with Mac-1. Taken together, these observations indicate that Mac-1 recruits a To ll/IL-1 receptor family-like cascade to modulate NF-kappaB activity. This r epresents a new pathway for integrin-dependent modulation of gene expressio n.