VCAM-1 is not involved in LPAM-1 (α₄β(p)/α₄β₇) mediated binding of lymphoma cells to high endothelial venules of mucosa-associated lymph nodes

The migration of lymphocytes from the blood into various lymphoid organs (lymphocyte homing) occurs in specialized high endothelial venules (HEV). Homing of lymphocytes into mucosa-associated lymph nodes in the mouse is mediated at least in part by the lymphocyte homing receptor LPAM-1, an integrin which has been identified as the heterodimer α₄β(p) (α₄β₇ in humans). The HEV-ligand for this integrin in the homing process has not yet been identified. VCAM-1, a cytokine-inducible, endothelial adhesion molecule for lymphocytes and monocytes, was recently demonstrated in vitro to be a ligand for the α₄β(p) integrin. We have tested whether VCAM-1 could be a candidate for an α₄β(p) ligand on HEV. Two findings strongly argue against this possibility: First, an anti-VCAM-1 monoclonal antibody (mAb) failed to block the binding of the mouse T-lymphona TK-1 to HEV in cryostat sections of mesenteric lymph nodes, even though this antibody blocked α₄β(p) mediated binding of TK-1 cells to VCAM-1 on TNF-α-activated mouse endothelioma cells. Second, expression of VCAM-1 on lymph node endothelium was undetectably low as tested by immunofluorescence staining of mouse tissue sections using four different mAbs against mouse VCAM-1, three of which are described in this report. Surprisingly, expression of VCAM-1 on lymph node endothelium was not found even in mice which had been treated systemically with high doses of TNF-α or LPS, although VCAM-1 expression was strongly induced on endothelia of all other organs that were analyzed. This demonstrates that lymph node endothelium differs from endothelia in other tissues in its regulation of the expression of VCAM-1.