Recruitment of leukocytes to the site of infection is an essential step in host defense during infectious diseases against invading pathogens. RAGE plays a role in the regulation of cell migration in several ways. First of all, RAGE is a counter-receptor for integrins on leukocytes; in particular, RAGE has been identifi ed as a binding partner for the β2 integrins, Mac-1 and p150, 95 [8] . Second, by the interaction of RAGE with β2 integrinmediated leukocyte recruitment in vivo: RAGE -/mice displayed a diminished number of adherent infl ammatory cells on the peritoneum after CLP [9] and a reduction in neutrophil infl ux in the peritoneal cavity after thioglycollate peritonitis [8] . Interestingly, HMGB1 can activate lateral (in cis) RAGE-Mac-1 interactions on the leukocyte cell surface, enhancing Mac-1-intercellular adhesion molecule (ICAM)-1-dependent adhesion and migration [27] (Fig. 1 , indicated by the blue line and blue "+"). Furthermore, a recent report shows that endothelial expressed RAGE acts in concert with ICAM-1 in mediating β 2 integrin-dependent leukocyte adhesion during acute trauma-induced infl ammation [28] (Fig. 1 , indicated by the green line and green "+").