E-SELECTIN MEDIATES LEUKOCYTE ROLLING IN INTERLEUKIN-1-TREATED RABBITMESENTERY VENULES

The selectins are lectin-like cell surface glycoproteins that have bee n implicated in playing a crucial role in the initiation of leukocyte adhesion to endothelial cells (ECs) during inflammation. Binding of se lectins under conditions of flow mediates leukocyte rolling, which in vivo is almost exclusively observed in venular microvessels. We have s hown in previous experiments that intraperitoneal treatment of rabbits with interleukin-1 beta (IL-1) increases leukocyte rolling in exterio rized mesenteries. In the present study, we used immunohistochemistry of mesenteries and found that IL-1 induced a marked E-selectin immunor eactivity, preferentially in venules. We therefore hypothesized that t he increased rolling in response to IL-1 may be related to the inducti on of E-selectin on venular ECs. Intravital microscopy was used to inv estigate interactions between leukocytes and ECs after intraperitoneal application of IL-1. The rabbit E-selectin monoclonal antibody (MoAb) 9H9 significantly reduced rolling of leukocytes by approximately 40%. Vehicle atone, class-matched control MoAb or the nonblocking anti-E-s electin MoAb 14G2 had no effect on rolling. These results indicate tha t leukocytes roll on inflamed venular ECs partly through interactions with E-selectin. Furthermore, we propose that the restricted E-selecti n immunoreactivity by venular ECs contributes to the remarkable differ ence seen between arterioles and venules in exhibiting leukocyte rolli ng in vivo. (C) 1994 by The American Society of Hematology.