VCAM-1 is not involved in LPAM-1 (alpha 4 beta p/alpha 4 beta 7) 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 alpha 4 beta p (alpha 4 beta 7 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 alpha 4 beta p integrin. We have tested whether VCAM-1 could be a candidate for an alpha 4 beta 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-lymphoma TK-1 to HEV in cryostat sections of mesenteric lymph nodes, even though this antibody blocked alpha 4 beta p mediated binding of TK-1 cells to VCAM-1 on TNF-alpha-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-alpha or LPS, although VCAM-1 expression was strongly induced on endothelial of all other organs that were analyzed.(ABSTRACT TRUNCATED AT 250 WORDS)
Hahne
M
M
Hans Spemann Laboratory, Max Planck Institute for Immunobiology, Freiburg/Germany.
Lenter
M
M
Jäger
U
U
Isenmann
S
S
Vestweber
D
D
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D004727:Endothelium / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006391:Hemangioma / Q000473:pathology; D016023:Integrins / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008198:Lymph Nodes / Q000166:cytology*; D016393:Lymphoma, B-Cell / Q000378:metabolism / Q000473:pathology*; D016399:Lymphoma, T-Cell / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009928:Organ Specificity; D010581:Peyer's Patches / Q000166:cytology*; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1; D014699:Venules
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D016023:Integrins; D008070:Lipopolysaccharides; D016201:Receptors, Lymphocyte Homing; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C071777:integrin alpha4beta7; D013755:Tetradecanoylphorbol Acetate