Mechanism of mononuclear cell activation by an anti-CD43 (sialophorin) agonistic antibody.
CD43 (sialophorin, gpL115) is a sialoglycoprotein expressed on a wide variety of blood cells including lymphocytes, monocytes, neutrophils, and platelets. L10, an 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.
Silverman
L B
LB
Division of Allergy and Immunology, Children's Hospital, Boston, MA 02115.
Wong
R C
RC
Remold-O'Donnell
E
E
Vercelli
D
D
Sancho
J
J
Terhorst
C
C
Rosen
F
F
Geha
R
R
Chatila
T
T
D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology*; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology; D017252:CD3 Complex; D002118:Calcium / Q000378:metabolism; D006801:Humans; D051917:Leukosialin; D008213:Lymphocyte Activation; D051379:Mice; D009000:Monocytes / Q000276:immunology; D010716:Phosphatidylinositols / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D015290:Second Messenger Systems; D012795:Sialoglycoproteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000502:physiology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D051917:Leukosialin; D010716:Phosphatidylinositols; D011948:Receptors, Antigen, T-Cell; C465014:SPN protein, human; D012795:Sialoglycoproteins; C497863:Spn protein, mouse; D002118:Calcium