SYNTHESIS AND REGULATION OF COMPLEMENT COMPONENTS BY HUMAN MONOCYTES MACROPHAGES AND BY ACUTE MONOCYTIC LEUKEMIA

Proteins of the complement system (C2, C3) are synthesized by human mo nocytes and macrophages, thus providing an important local source of t hese proteins in vivo which serve as a first-line host defense mechani sm. In this study, we investigated the production of complement compon ents C2, C4, and C9 by human monocytes/macrophages and by the patholog ic cells of scute monocytic leukemia which represent a source of immat ure monocytic precursors. Human blood monocytes were collected and pur ified by cytapheresis and elutriation and leukemic cells by Ficoll gra dient. Secretion of complement components was measured by a hemolytic assay. The evaluation of the mRNAs of the various complement component s in the cells was performed by polymerase chain reaction (PCR) by add ing P-32 labeled deoxycytidinetriphosphate (dCTP) to the amplification step. Functional C2 was found to increase during in vitro maturation of macrophages up to the fourth week of culture. C2 mRNA was detected after amplification and increased during the maturation. Interferon-ga mma (IFN-gamma) mediated a marked increase of the C2 mRNA. We found a decrease in synthesis of C4 mRNA during in vitro differentiation of hu man monocytes. The effect of IFN-gamma resulted in an increase in C4 m RNA. C9 mRNA was not detected although it was detected in the HepG2 he patoma-derived cell tine. Functional C2 was not detected by leukemic c ells after 24 h of culture but little functional C4 was present in the cell supernatants. As they were by human monocytes and macrophages, C 2 and C4 mRNAs were detected after amplification but C9 mRNAs were not detected. In this study we showed that human monocytes and macrophage s synthesize the functional C2 and C4 complement components that are r egulated by IFN-gamma. On the other hand, they do not express C9 mRNA, indicating that the membrane attack complex of complement cannot be a ssembled by these cells. According to these results, C2 and C4 gene ex pression occurs in the pathologic cells of acute monocytic leukemia; h owever, these cells are unable to assemble the membrane attack complex .