Modulation of human lymphocyte function by C3a and C3a(70-77).
Human C3a and the synthetic octapeptide C3a (70-77), which retains the activities of an anaphylatoxin, inhibit in a concentration-dependent manner the generation of leukocyte inhibitory factor (LIF) activity by human mononuclear leukocytes and T lymphocytes cultured with the mitogens phytohemagglutinin (PHA) or concanavalin A (Con A) or the antigen streptokinase-streptodornase (SK-SD). The generation of LIF activity was inhibited by 50% by 10(-8) M C3a or C3a(70-77) with PHA or Con A as the stimulus, whereas a more than 10-fold higher concentration of C3a(70-77) than C3a was required to achieve the same level of suppression with SK-SD as the stimulus. Similar concentrations of C3a(70-77) inhibited to the same extent the migration of T lymphocytes stimulated by alpha-thioglycerol of Con A. Neither C3a nor C3a(70-77) altered significantly the uptake of [3H]thymidine by human mononuclear cells exposed to PHA, Con A, or SK-SD. The capacity of C3a(70-77)-Sepharose,m but not Sepharose alone, to adsorb or inactivate mononuclear leukocytes required for the generation of LIF activity established a direct interaction. Analysis of the lymphocytes in the effluent from C3a(70-77)-Sepharose columns, using monoclonal antibodies to surface antigens, showed a selective depletion of the helper/inducer population of lymphocytes. C3a might represent an important mediator of the functionally selective regulation of human T lymphocyte activities by the complement system.
D002455:Cell Division; D002465:Cell Movement; D002470:Cell Survival; D003176:Complement C3 / Q000494:pharmacology*; D015926:Complement C3a; D003208:Concanavalin A / Q000494:pharmacology; D006801:Humans; D007961:Leukocyte Migration-Inhibitory Factors / Q000096:biosynthesis*; D008214:Lymphocytes / Q000502:physiology*; D008222:Lymphokines / Q000096:biosynthesis*; D010835:Phytohemagglutinins / Q000494:pharmacology; D013299:Streptodornase and Streptokinase / Q000494:pharmacology; D013601:T-Lymphocytes / Q000502:physiology*
D003176:Complement C3; D007961:Leukocyte Migration-Inhibitory Factors; D008222:Lymphokines; D010835:Phytohemagglutinins; D003208:Concanavalin A; C035531:complement C3a, (70-77); D015926:Complement C3a; D013299:Streptodornase and Streptokinase