CD45 Engagement Induces L‐Selectin Down‐Regulation

Abstract

The CD45 glycoprotein isoforms exhibit a receptor-like composition and display intracellular protein tyrosine phosphatase (PTPase) activity. The present study links CD45 to the regulation of L-selectin (CD62L), a leucocyte glycoprotein important for extravasation and homotypic aggregation. Monoclonal antibodies (MoAbs) IOL1b and AICD45.2, but not GAP8.3, all of which are directed against common CD45 epitopes, were found to elicit lymphocyte L-selectin down-regulation. Lymphocyte L-selectin down-regulation in response to anti-CD45 MoAbs was enhanced by high cell density and partially antagonized by the protein tyrosine kinase (PTK) inhibitor, herbimycin A. The MoAbs IOL1b, AICD45.2 and GAP8.3 recognized granulocyte-expressed CD45 but did not induce loss of L-selectin expression of granulocytes. In contrast, the CD45 PTPase inhibitor, vanadate, induced L-selectin down-regulation both in lymphocytes and granulocytes. The PTPase activation by nitric oxide (NO) or the NO-generating compound, sodium nitroprusside, did not affect L-selectin surface expression. Increased concentrations of soluble L-selectin were detected after anti-CD45 or vanadate-induced down-regulation of L-selectin surface expression. While activation of protein kinase C (PKC) by phorbol 12-myristate 13-acetate (PMA) induces rapid L-selectin down-regulation of L-selectin surface expression in both lymphocytes and granulocytes, the PKC inhibitor, H 7, was also found to down-regulate lymphocyte and granulocyte L-selectin surface expression. The inhibitor H 7 synergized with vanadate in down-regulating lymphocyte L-selectin surface expression, but partially inhibited vanadate-induced granulocyte L-selectin down-regulation. The results suggest that in a cell type-specific fashion the PKC system and tyrosine phosphorylation and dephosphorylation cascades are involved in the regulation of L-selectin surface expression.

CD45 Deficiency Drives Amyloid-β Peptide Oligomers and Neuronal Loss in Alzheimer's Disease Mice

“…In the periphery, CD45 promotes antigen-specific B- and T-cell responses by dephosphorylating Src-family kinases (Thomas and Brown, 1999; Penninger et al, 2001). CD45 plays additional roles in regulating selectin expression (Stibenz et al, 1996; Wroblewski and Hamann, 1997) and integrin function (Roach et al, 1997; Shenoi et al, 1999). CD45 has also been shown to negatively regulate cytokine receptor-mediated signaling via Janus associated kinases (Irie-Sasaki et al, 2001), revealing yet another role of CD45 in dampening overly exuberant immune responses.…”

Cell-surface expression of L-selectin (CD62L) by blood lymphocytes: Correlates with affective parameters and severity of panic disorder

“…A substantial subset of extravascular T-cells in nonlymphoid tissues are "memory" T-cells and show diminished expression of CD45RA and CD62L [Mackay et al, 1990;Marathias et al, 1991]. Engagement of CD45 by its ligand induces the down-regulation of L-selectin [Stibenz et al, 1996].…”

The phenotypic profile of CD34‐positive peripheral blood stem cells in different mobilization regimens

“…1 cells as downregulation of L-selectin on mature cells takes place after cell activation (Stibenz et al, 1996). The lower expression of the adhesion molecule CD54 (ICAM-1) found on the CD34 1 cells in group III might impair interactions between these stem cells and stroma after the first steps of homing, as can be inferred from an earlier study (Rao et al, 1996).…”

“…CD11b expression showed a large increase in all three cases after the second mobilization course. In mature myeloid cells, an increase in CD11b expression is often accompanied by a decrease in L-selectin expression (Stibenz et al, 1996). However, the expression of L-selectin on the CD34 1 cells in the whole blood samples remained equally high in all three cases.…”