EFFECTS OF COMPLEMENT ACTIVATION PRODUCTS ON THE SYNTHESIS OF DECAY-ACCELERATING FACTOR AND MEMBRANE COFACTOR PROTEIN BY HUMAN MESANGIAL CELLS

We previously demonstrated that activation of terminal complement comp onents (C8 and/or C9) increases the synthesis and expression of decay accelerating factor (DAF) on human glomerular cells. DAF is a cell mem brane-associated complement regulatory protein that inhibits complemen t activation on cell surfaces. In the present studies we evaluated, fi rst, the mechanisms by which complement activation stimulates DAF synt hesis, and second, the effect of complement activation on the synthesi s, and expression of membrane cofactor protein (MCP), another compleme nt regulatory protein, by human mesangial cells (HMC) in culture. Comp lement activation by immune complexes resulted in increased DAF mRNA l evels by at least two mechanisms: deposition of activated C3 on HMC an d generation of soluble complement activation products, specifically C 5a. The increase in DAF mRNA levels induced by activated C3 or C5a was short lived (less than 4 hr). In contrast, the up-regulation of DAF m RNA levels induced by activation of the complete complement cascade pe rsisted for at least eight hours. The effect of complement activation on DAF mRNA levels was not affected by cycloheximide, a protein synthe sis inhibitor. However, cycloheximide alone resulted in a significant upregulation of DAF mRNA levels on HMC. In contrast to those findings, complement activation did not cause an up-regulation of MCP mRNA, nor an increase in the synthesis of this protein. However, by FACS, compl ement produced a small but significant increase of MCP protein levels on HMC. In conclusion, both MCP and DAF are present on HMC. Several ac tivated complement components are capable of increasing DAF mRNA level s, but DAF protein levels increase only after activation of the whole complement cascade. Complement activation has no effects on the synthe sis of MCP.