biostudies-literatureWolf DNHLBI NIH HHS1269-79https://www.ebi.ac.uk/biostudies/studies/S-EPMC3291815biostudies-literatureUnknown109(11)<h4>Rationale</h4>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.<h4>Objective</h4>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.<h4>Methods and results</h4>CD40L concentration-dependently bound to Mac-1 I-domain in solid phase binding assays, and a high-affinCirculation researchBinding 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.PMC3291815R01 HL061589R01 HL034636HL 34636R37 HL034636Wiedemann AHoppe NStachon Pvon zur Muhlen CBlankenbach HDuerschmied DZeschky KRodriguez AOPeter KBassler NHerr NSoloviev DAZhang LPlow EFHilgendorf IZirlik AWolf DMarchini TBledzka KWillecke FLibby PGutte KHohmann JDBode CfalseBinding 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.<h4>Rationale</h4>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.<h4>Objective</h4>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.<h4>Methods and results</h4>CD40L concentration-dependently bound to Mac-1 I-domain in solid phase binding assays, and a high-affin2011-01-01T00:00:00Z2011 Nov2026-04-30T20:58:08.21Z2019-03-27T00:49:42ZS-EPMC32918152199832610.1161/CIRCRESAHA.111.24768410.1161/circresaha.111.247684