Monocyte migration to inflamed skin and lymph nodes is differentially controlled by L-selectin and PSGL-1

Monocyte recruitment and differentiation into dendritic cells or macrophages play a critical role in defense mechanisms against pathogens and in inflammatory and autoimmune diseases. Important contributions have been made on the molecular events controlling neutrophil and lymphocyte extravasation under steady state or inflammation. However, the molecules involved in monocyte rolling during their migration to antigen capture areas and lymphoid organs during infection remain undefined. Here we have analyzed the homing molecules controlling mouse monocyte rolling in an experimental model of Leishmania major infection. Monocyte migration through inflamed dermal venules was dependent on interactions of PSGL-1 with P- and E-selectins, and of L-selectin with PNAd, whereas migration through lymph node high endothelial venules relied essentially on L-selectin-PNAd interactions. These results might have important implications regarding the induction of immune responses against pathogens and future immunotherapeutic protocols of inflammatory and autoimmune diseases, based on selective inhibition of monocyte migration to specific inflammatory foci.