Overlapping roles for L-selectin and P-selectin in antigen-induced immune responses in the microvasculature

Although L-selectin mediates lymphocyte attachment to endothelial venules o f peripheral lymph nodes, its role in leukocyte recruitment into tissues fo llowing Ag challenge is less well established. The objective of this study was to systematically examine the role of L-selectin in leukocyte rolling i n the peripheral microvasculature during the first 24 h of an immune respon se. A type I hypersensitivity response was elicited in wild-type (C57BL/6) and L-selectin-deficient mice by systemic (i.p.) sensitization and intrascr otal challenge with chicken egg OVA. The cremaster microcirculation was obs erved in untreated and sensitized mice 4, 8, and 24 h post-Ag challenge by intravital microscopy, Leukocyte recruitment in L-selectin-deficient mice a nd wild-type mice treated with an L-selectin function-blocking mAb was exam ined at each time point. Ag challenge induced a significant increase in leu kocyte rolling (60 cells/min/venule to similar to 300 cells/min/venule) in wild-type mice at 4-24 h, This response was reduced by approximately 60-70% in L-selectin-deficient mice and in wild-type mice treated with an L-selec tin-blocking mAb, P-selectin blockade by Ab completely inhibited leukocyte rolling at 4-24 h in wild-type animals and also blocked the residual rollin g seen in L-selectin-deficient mice. Blocking E-selectin function had no ef fect on leukocyte rolling flux at any time point in wild-type or L-selectin -deficient mice. Despite reduced rolling, leukocyte adhesion and emigration were not measurably reduced in the L-selectin-deficient mice in this vascu lar bed. In conclusion, leukocyte rolling is L-selectin-dependent post-hg c hallenge with L-selectin and P-selectin sharing overlapping functions.