EVIDENCE FOR AN ACTIVE HYDROPHOBIC FORM OF FACTOR-H THAT IS ABLE TO INDUCE SECRETION OF INTERLEUKIN-1-BETA OR BY HUMAN MONOCYTES

We studied the capacity of human factor H to promote the secretion of a lymphocyte-activating factor (LAF) by human monocytes cultured under serum-free conditions. Presence of LAF in the culture supernatants was assessed with the mouse thymocyte assay. Highly purified factor H alone had no effect on thymocyte proliferation. When monocytes were cultured with factor H for 24 h. a significant secretion of LAF was observed. The effect was dose dependent over a range of factor H concentrations from 1 to 15-mu-g/ml. Polymyxin B did not abrogate the capacity of factor H to induce LAF secretion. Adsorption of factor H preparations onto anti-factor H-Sepharose completely suppressed the phenomenon. Conversely, the activity was recovered in the acidic eluate. Furthermore, factor H subpopulation PHI-2, that was able to bind to phenyl-Sepharose, was a stronger inducer of LAF secretion by monocytes than the subpopulation PHI-1 (which did not bind to phenyl-Sepharose). Using a specific radioimmunoassay for interleukin 1-beta (IL 1-beta), we observed a good correlation between the LAF activity and the amount of IL 1-beta secreted by human monocytes stimulated with factor H. We have shown previously that factor H (PHI-2) bound specifically on Raji cells whereas factor H (PHI-1) did not. These results argue for the participation of the interaction of factor H with its receptor to stimulate the secretion of IL 1 by monocytes and that the PHI-2 form of factor H is a ligand for the human factor H receptor.