Complement-Mediated Tissue Damage: Contribution of the Classical and Alternate Complement Pathways in the Forssman Reaction

Abstract The contribution of the classical and alternate complement pathways to complement-mediated tissue damage in the Forssman reaction was studied in a strain of C4D guinea pigs with a nonoperative classical pathway, but an intact alternate pathway. It was found that the C4D guinea pigs were resistant to the Forssman reaction, but that reconstitution of the classical pathway by the administration of normal guinea pig serum as a source of C4 restored the deficient animals' susceptibility to the toxic effects of injected Forssman antiserum. C4D animals with a restored C4 level only developed the Forssman reaction if the Forssman antiserum was injected many hours after the injection of C4. Thus, a period of time was required for C4 to distribute within the extravascular compartment. These results indicate that interaction of anti-Forssman antibody with extravascular Forssman antigen and complement is necessary for lethality, and that vascular endothelial damage cannot alone account for the pathogenesis of the Forssman reaction, as previously believed. The results also indicate that intravascular C4 is not freely available to tissue sites.