CD45-mediated signals can trigger shedding of lymphocyte L-selectin.
The adhesion molecule L-selectin is proteolytically cleaved from the surface of lymphocytes and neutrophils within minutes after stimulation by phorbol ester or calcium ionophores. In contrast to neutrophils, soluble factors have not been shown to induce down-regulation of L-selectin on lymphocytes. We therefore examined whether signals generated by interaction with cell surface receptors could deliver physiological stimuli inducing this regulatory mechanism. While cross-linking of several adhesion molecules (CD2, CD44, alpha 4-integrin, LFA-1) by antibody did not result in a significant reduction of the expression of L-selectin, antibodies against CD45 and Thy-1.2, both involved in the regulation of lymphocyte activation, induced loss of cell surface L-selectin within minutes, even at 4 degrees C, by shedding into the supernatant. Cross-linking of these molecules was shown to be essential, but Fc interactions or adherent cells were not required. A similar response, albeit less effective, was found after cross-linking of CD3. Interestingly, initiation of shedding only occurred in the presence of cell-cell contact, pointing to a second, as yet unknown, signal required. Loss of L-selectin induced by CD45 cross-linking is followed by a rapid re-expression of the molecule upon incubation at 37 degrees C. This reaction is also dependent on specific triggering signals as rapid re-expression was not observed after removal of L-selectin by trypsin. The data indicate that the protein phosphatase CD45 as well as the TCR complex itself in combination with a further, as yet unknown, cell-cell contact-dependent stimulus have a regulatory role in the dynamic control of L-selectin expression in lymphocytes.
Wroblewski
M
M
Abt. für Immunologie, Medizinische Klinik, Universitätskrankenhaus Eppendorf, Hamburg, Germany.
Hamann
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002450:Cell Communication / Q000276:immunology; D002462:Cell Membrane / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D007694:Killer Cells, Natural / Q000378:metabolism; D019041:L-Selectin / Q000378:metabolism*; D017493:Leukocyte Common Antigens / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D016131:Lymphocyte Subsets / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D015398:Signal Transduction / Q000276:immunology*
D000911:Antibodies, Monoclonal; D019041:L-Selectin; D017493:Leukocyte Common Antigens