Mechanism of mononuclear cell activation by an anti-CD43 (sialophorin) agonistic antibody

L. B. Silverman, R. C.K. Wong, E. Remold-O'Donnell, D. Vercelli, J. Sancho, C. Terhorst, F. Rosen, R. Geha, T. Chatila

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Abstract

CD43 (sialophorin, gpL115) is a sialoglycoprotein expressed on a wide variety of blood cells including lymphocytes, monocytes, neutrophils, and platelets. L10, and anti-CD43 mAb, has been shown to induce monocyte-dependent activation and proliferation of human T lymphocytes. We have studied the signaling mechanism involved in this activation process. Treatment of PBMC and purified populations of T cells and monocytes with L10 induced the hydrolysis of phosphoinositides with the resultant generation of the phosphoinositide-derived second messengers diacylglycerol and inositol phosphates. This was associated with the translocation of protein kinase C from cytosol to membrane fractions and an increase in free intracellular Ca2+ in treated cells. In human leukemic T cell lines, the magnitude of signaling via CD43 did not correlate with the density of the TCR/CD3 surface expression nor with the intensity of signaling via the TCR/CD3. Moreover, a mutant derived from the leukemic T cell line HPB-ALL that was severely defective in TCR/CD3 surface expression and signaling nevertheless had normal CD43 surface expression and signaling compared with the parent cell line. It is concluded that CD43 is functionally coupled to the phospholipase C/phosphoinositides signaling pathway. In human T cells, signaling via CD43 proceeds independently of TCR/CD3. The widespread expression of CD43 suggests a potentially important role for this molecule in orchestrating the activation of multiple cell types.

Original languageEnglish (US)
Pages (from-to)4194-4200
Number of pages7
JournalJournal of Immunology
Volume142
Issue number12
StatePublished - Jan 1 1989
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Silverman, L. B., Wong, R. C. K., Remold-O'Donnell, E., Vercelli, D., Sancho, J., Terhorst, C., Rosen, F., Geha, R., & Chatila, T. (1989). Mechanism of mononuclear cell activation by an anti-CD43 (sialophorin) agonistic antibody. Journal of Immunology, 142(12), 4194-4200.