Modulation of P-selectin dependent leukocyte-endothelial cell interactions by inducible heme oxygenase in rat post-capillary venules in vivo

This study aimed to examine whether induction of heme oxygenase-1 limits endothelial cell-leukocyte interactions in vivo. Leukocyte traffics were visually monitored in rat mesenteric post-capillary venules under monitoring regional erythrocyte velocity using intravital video microscopy. In the control rats, rolling and stationally adhesion of leukocytes in venular endothelium were elicited in response to superfusion with 500μM H ₂O ₂ without showing a reduction of shear rates. These changes were abolished by pretreatment with an anti-rat P-selectin MoAb ARP2.4. In addition, laser confocal microfluorography assisted by fluorescence-labelled ARP2.4 revealed that the H ₂O ₂ superfusion enhanced the P-selectin expression in venules. When rats were pretreated for 12 hrs with an intraperitoneal injection of hemin, microvascular endothelium as well as parenchymal cellular components including mast cells displayed a marked expression of HO-1. Under these circumstances, the H ₂O ₂-elicited endothelial cell-leukocyte interactions were attenuated almost completely. On the other hand, superfusion with 0.1 μM zinc protoporphyrin IX, an inhibitor of HO, restored the H ₂O ₂-elicited P-selectin expression and subsequent adhesive responses of leukocytes. The present findings thus suggest that HO-1 induction modulates endothelium-leukocyte interaction in vivo.