Different mechanisms regulate the monoclonal antibody-induced modulation of CD2, CD3, and CD5 in human lymphocytes.
The CD2, CD3, and CD5 antigens are down-modulated from the cell surface of peripheral blood mononuclear cells after a 24-hr incubation with specific monoclonal antibodies (mAb). Here we show that active (phorbol myristate acetate, phorbol dibutyrate acetate, and mezerein) but not inactive (4 beta-phorbol) tumor-promoting agents inhibit the mAb-induced modulation of CD2 and CD5, but not CD3, without concomitant changes in the surface distribution of these antigens (such as capping). This inhibitory effect is not protein synthesis dependent and is reversed by protein kinase C inhibitors (staurosporine and H-7). The use of cytoskeleton-disrupting agents shows the existence of different cytoskeletal interactions driving the mAb-induced modulation of CD2 and CD5 with respect to CD3. Treatment with cytochalasin D (an agent that inhibits microfilament polymerization) but not colchicine (an agent that inhibits microtubule polymerization) reproduced the effect of TPA on the mAb-induced modulation of CD2, CD3, and CD5. Our results indicate that the mAb-induced modulation of CD2 and CD5 is dependent on microfilament (namely actin) polymerization and PKC activation, while the modulation of CD3 is not.
Alberola-Ila
J
J
Servei d'Immunologia, Hospital Clinic i Provincial de Barcelona, Spain.
Places
L
L
Fabregat
V
V
Vives
J
J
Lozano
F
F
D000911:Antibodies, Monoclonal / Q000276:immunology*; D016525:Antigenic Modulation / Q000187:drug effects*; D015703:Antigens, CD / Q000378:metabolism*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D018801:CD2 Antigens; D017252:CD3 Complex / Q000378:metabolism*; D018956:CD5 Antigens; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008213:Lymphocyte Activation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011971:Receptors, Immunologic / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D017252:CD3 Complex; D018956:CD5 Antigens; D011971:Receptors, Immunologic; D015638:Cytochalasin D; D011493:Protein Kinase C; D017493:Leukocyte Common Antigens; D013755:Tetradecanoylphorbol Acetate