Binding of CD40L to Mac-1's I-domain involves the EQLKKSKTL motif and mediates leukocyte recruitment and atherosclerosis--but does not affect immunity and thrombosis in mice.

ABSTRACT:

Rationale

CD40L figures prominently in chronic inflammatory diseases such as atherosclerosis. However, since CD40L potently regulates immune function and hemostasis by interaction with CD40 receptor and the platelet integrin GPIIb/IIIa, its global inhibition compromises host defense and generated thromboembolic complications in clinical trials. We recently reported that CD40L mediates atherogenesis independently of CD40 and proposed Mac-1 as an alternate receptor.

Objective

Here, we molecularly characterized the CD40L-Mac-1 interaction and tested whether its selective inhibition by a small peptide modulates inflammation and atherogenesis in vivo.

Methods and results

CD40L concentration-dependently bound to Mac-1 I-domain in solid phase binding assays, and a high-affin

SUBMITTER: Wolf D 

PROVIDER: S-EPMC3291815 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature