Leukocyte Integrin Mac-1 Recruits Toll/Interleukin-1 Receptor Superfamily Signaling Intermediates to Modulate NF-κB Activity

Can Shi, Xiaobin Zhang, Zhiping Chen, Martyn K. Robinson, Daniel I. Simon
2001 Circulation Research  
The leukocyte integrin Mac-1 (␣M␤2, CD11b/CD18) regulates important cell functions in inflammation, including adhesion, phagocytosis, and oxidative burst. Deficiency of Mac-1 reduces vessel wall inflammation and neointimal thickening after murine carotid artery injury. Although Mac-1 has been implicated in modulating AP-1 and NF-B activity, the signal transduction pathways involved are undefined. cDNA array analysis of Mac-1-clustered compared with -nonclustered monocytic THP-1 cells showed
more » ... -1 cells showed increased expression of the signal transducer TRAF6 (TNF receptor-associated factor 6), leading us to consider the possibility that Mac-1 used a Toll/IL-1 receptor family-like signaling pathway. Mac-1-dependent activation of NF-B was potentiated by wild-type, and attenuated by dominant negative, TRAF6-and TGF-␤-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 Toll/IL-1 receptor family-like cascade to modulate NF-B activity. This represents a new pathway for integrin-dependent modulation of gene expression. (Circ Res. 2001;89:859-865.)
doi:10.1161/hh2201.099166 pmid:11701612 fatcat:eyl3sz4mqfhftdu3vbfuvvkk3a