Leukocyte recruitment in contact sensitivity
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AbstractContact sensitivity is an inflammatory disorder characterized by leukocyte recruitment. We used intravital microscopy to directly visualize leukocyte rolling and adhesion. By blocking specific adhesion molecules, we elucidated the molecular mechanisms mediating early leukocyte recruitment to be E- and P-selectin and then demonstrated that leukocyte recruitment in the late phase had a different adhesive profile (mainly a4- integrin). Complete blockade of E- and P-selectin within the first 2 hours of leukocyteendothelial cell interactions eliminated selectin-independent leukocyte recruitment at 24 hours. Specific elimination of CD4, lymphocytes in the early phase eliminated the late response. Addition of these same CD4+ lymphocytes two hours after antigen challenge was too late for these cells to home to the skin. We further established that mast cells act to modulate the T-lymphocyte response in CS. In the absence of mast cells, T1-1l cells preferentially adhere to vascular endothelium, whereas T112 cells preferentially adhere in wild-type mice.
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