Varying roles of E-selectin and P-selectin in different microvascular bedsin response to antigen

Expression of E-selectin and P-selectin is critical in the effector phase o f leukocyte recruitment in response to Ag, Whether their relative roles dif fer between tissues in response to the same Ag is unknown. In this study, a type I hypersensitivity response was elicited in C57BL/6 mice by systemic sensitization with OVA, Following local Ag challenge, endothelial selectin expression was examined in the skin and cremaster muscle microvasculature u sing a dual-radiolabeled mAb technique. Next, the dermal and muscle microci rculations were visualized using intravital microscopy to establish roles f or P-selectin and/or E-selectin, In untreated mice, leukocyte recruitment i n both skin and skeletal muscle was mediated entirely by P-selectin, Follow ing Ag challenge, leukocyte rolling flux and adhesion were dramatically inc reased and leukocyte rolling velocity was unchanged in muscle. Only P-selec tin expression increased in muscle, and leukocyte recruitment was entirely dependent upon this selectin, In contrast, in Ag-challenged skin, leukocyte rolling flux did not increase, but rolling velocity dropped profoundly. In skin, only E-selectin expression increased, and blockade of either E-selec tin or P-selectin had minimal effect on either rolling flux or rolling velo city. Blockade of both selectins reduced rolling Bur by 80% and increased r olling velocity sevenfold. These data highlight striking differences in exp ression of the endothelial selectins in separate microvascular beds in resp onse to the same stimulus and demonstrate that these differences underlie v ery different patterns of leukocyte recruitment. The data underscore the im portance of studying individual microvascular beds to understand tissue-spe cific leukocyte recruitment in vivo.