The role of macrophages in the regulation of high endothelial venule expression within the peripheral lymph nodes of mice exposed to ultraviolet radiation.

A number of direct and indirect immunologic consequences follow the exposure of the skin to ultraviolet radiation (UVR). One of the remote effects of UVR is the increased accumulation of lymphocytes within peripheral lymph nodes that drain irradiated skin sites. The present study was designed to evaluate the mechanisms responsible for this increased lymphocyte accumulation. Primary lymphocyte localization into draining regional lymph nodes was found to be markedly increased (up to 81%) by UVR exposure of the skin. The changes in lymphocyte localization correlated closely with increases in the number and density of lymphocyte-receptive endothelial structures (high endothelial venules, or HEV) within these regional lymph nodes. Because macrophages or their products are believed to maintain resting HEV expression and function, we assessed the role of these cells in the expansion of HEV due to UVR exposure. Our studies demonstrated that a peripheral injection of antigen-activated macrophages caused an increase in HEV expression within lymph nodes draining the injection site. Conversely, treatment of mice with silica or carrageenan to depress macrophage function produced both histologic and functional hyporesponsiveness of the microvascular endothelium to UVR-stimulated HEV expansion. These changes in endothelial cell responsiveness correlated with the absolute number of MAC-1+ cells present within the regional nodes of UVR-exposed mice. Our studies have demonstrated a striking similarity between lymph node microvascular changes in response to cutaneous UVR- and antigen-exposure. We therefore suggest that macrophage-mediated signals may initiate a general mechanism that increases lymphocyte recirculation through the regional lymph nodes in response to both antigenic and inflammatory challenge.