THE EXPERIMENTS PRESENTED HERE UTILIZE A HUMAN SERUM MARKEDLY DEFICIENT IN HEMOLYTIC COMPLEMENT ACTIVITY TO SHOW THAT: (a) The hemolytic deficiency is the result of a selective deficiency in hemolytic C1. (b) The relative absence of hemolytic C1 is due to a profound deficit in C1r function associated with less than normal C1s protein and hemolytic function and normal C1q protein concentration and function. This deficit in C1r in the face of normal C1q suggests that different cell types are responsible for the synthesis of each of these components. (c) Whatever the basis for the deficiency of C1r function, this defect results in an inadequate association of the remaining C1 subcomponents, C1q and C1s, even in the presence of calcium ions, thus suggesting that C1r has an important role in the assembly and/or maintenance of macromolecular C1.

Adolescent↗

PubMed1970

Interactions of the complement system with endotoxic lipopolysaccharides in immunoglobulin-deficient sera.

Bacterial lipopolysaccharides (LPS) derived from a variety of organisms effectively induced C consumption in humans, bovines, and porcines with developmental agammaglobulinemia; birds with experimental agammaglobulinemia; and humans with agammaglobulinemia syndromes. This interaction proceeded even in precolostral piglet sera which contained less than 2.5 x 10(-6) mg/ml gamma globulin, and led to generation of neutrophil chemotactic factor and anaphylatoxin in these sera. Hence, the LPS-C interaction can proceed in sera markedly deficient in immunoglobulin. The question of whether immunoglobulins can be bypassed in the LPS-C interaction, or whether they are regularly utilized in a way so efficient that their participation is masked, was considered.

Agammaglobulinemia↗

PubMed1970

Complement and complement-like activity in lower vertebrates and invertebrates.

A purified cobra venom factor with C-inhibiting activity also promotes lysis of erythrocytes in fresh mammalian serum. Lysis-inducing activity of purified cobra venom factor was found in sera of lower vertebrates including the cyclostome hagfish and in invertebrates. Lysis-inducing activity was most effective with frog serum. Frog serum was found to be more hemolytic for E(s) in the presence of CVF than when cells were sensitized with hemolysin. The hemolysis induced by CVF with frog serum, as in the higher vertebrates, was inhibited when sera were pretreated with known C inhibitors including heat, chelators, endotoxin, immune complexes, and CVF itself. Complexes formed with CVF and either frog serum or invertebrate hemolymph promoted lysis of indicator cells in the presence of frog serum in EDTA. This lysis was most marked when the starfish-CVF complex was used and was C-dependent. Conversely, complex formed with frog serum and CVF promoted lysis of E in the presence of invertebrate hemolymph (Limulus) in EDTA. Hence, serum components were to some degree at least interchangeable between vertebrate sera and invertebrate hemolymph. Lysis-inducing activity of purified CVF occurs in a wide range of species, has revealed activities resembling those of terminal C-components in lower vertebrates and invertebrates, and provides one means for study of C and C-like activities in primitive species.

Amphibians↗