No abstract

At least 3 complement factors were found necessary for the conversion of the thermolabile intermediate complex EAC'1a,4,2a to a thermostable state. One of these factors is the earlier described ß1C-globulin. The second, a heretofore unrecorded serum protein, ß1F-globulin. The third factor has not yet been defined as a discrete serum protein entity. Kinetic experiments indicated that ß1C reacted prior to ß1F, which in turn seemed to precede the third factor in the reaction sequence. Therefore, the 3 components were tentatively designated the third (C'3), the fifth (C'5), and the sixth (C'6) components of complement, respectively. A procedure was developed allowing the isolation of highly purified ß1C-(C'3) and ß1F-globulin (C'5) and of partially purified C'6. With respect to its function in immune hemolysis, ß1F-globulin or C'5 was found to be closely dependent on the simultaneous presence of C'6. The hypothesis that C'5 and C'6 form a functional unit was supported by the finding that both components interact with each other in solution resulting in the formation of a complex. A similar complex was also found in fresh human serum.

We studied monocyte function in a case of malakoplakia in an attempt to characterize the immune defect in this condition. Our patient's intracellular cyclic-GMP levels were abnormally low (mean +/- S.D. of 0.17 +/- 0.05 pmol per 10(7) malakoplakia cells, versus 0.79 +/- 0.12 in normals) p less than 0.001). After phagocytosis, his monocytes failed to release beta-glucuronidase. In the bactericidal assay, incubation of the patient's monocytes with Escherichia coli allowed growth of 542 +/- 46 colonies, normal monocytes allowed 95 +/- 22 (p less than 0.001). The percentage of monocytes with large lysosomal granules was 23 +/- 4 in the patient and 4 +/- 2 in normal controls. After in vitro incubation of the patient's cells or in vivo treatment with bethanechol chloride, the cyclic-GMP levels, bactericidal ability and lysosomal granules of the cells returned to normal levels. Low levels of cyclic-GMP could impair lysosomal function and bacterial killing in this condition. Cholinergic agonists correct the in vitro abnormalities and are beneficial in vivo.