Antibody restores human alternative complement pathway activation by mouse erythrocytes rendered functionally deficient by pretreatment with pronase.
Activation of the human alternative pathway of complement (C) by surfaces requires the initial deposition of C3b by fluid-phase C3 convertase and sustained C3 cleavage by C3 convertases fixed to the surface. Nonactivating particles have previously been characterized by an inability to sustain the function of C3 convertases on their surfaces because these sites were susceptible to the regulatory action of the control proteins. Pronase converts the mouse erythrocyte (E) from an activator to a nonactivator by markedly decreasing the ability of the cell to affix C3b generated by a fluid-phase C3 convertase; this conversion is unrelated to the action of the control proteins on bound C3b. The capacity of antibody and its F(ab')2 or Fab' fragments to restore the alternative pathway-activating function of pronase-treated mouse E indicates that the contribution of antibody is mediated by its combining site without a requirement for bridging or for the Fc portion. The fab'-dependent activation of the alternative pathway of C relates to the deposition of C3b on the particle surface, which is a first and continuing step in alternative pathway activation. The antibody effect is not directed to the action of the regulatory proteins. Thus, particle-dependent activation of the alternative C pathway has been shown for the first time to be abolished and restored by cell surface-directed mechanisms that function independently of the regulatory proteins.
D000818:Animals; D000906:Antibodies; D003167:Complement Activation; D050577:Complement C3-C5 Convertases / Q000378:metabolism; D003179:Complement C3b / Q000276:immunology / Q000378:metabolism; D003170:Complement Pathway, Alternative; D004912:Erythrocytes / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D051379:Mice; D008815:Mice, Inbred Strains; D011402:Pronase / Q000494:pharmacology*
D000906:Antibodies; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D003179:Complement C3b; D050577:Complement C3-C5 Convertases; D011402:Pronase