Generation of a unique fibroblast-activating factor by human monocytes

Purified human monocytes incubated with phytohemagglutinin (PHA), bacterial lipopolysaccharide (LPS), or serum-opsonized zymosan particles (OZ) generate human dermal fibroblast-activating activity, as assessed by increased fibroblast incorporation of [3H]-thymidine. A maximum concentration of fibroblast-activating activity was attained within 4 hr with OZ, whereas similar maximum levels required 12 hr with LPS and PHA. Sonicates of unstimulated monocytes had only minimal activity and the protein synthesis inhibitor cycloheximide suppressed significantly the appearance of fibroblast-activating activity, suggesting that the factors are generated prior to release. Filtration of supernates from OZ-stimulated monocytes on Sephadex G-75 yielded polydisperse fibroblast-activating activities, of which the major factors exhibited a mol. wt. of approximately 60,000 and 10,000. The supernates from PHA-stimulated monocytes had one predominant factor, termed fibroblast-activating factor of monocytes (FAF-M), with an apparent mol. wt. of 38,000 and a minor activity with a mol. wt. of 10,000. FAF-M was composed of two principles with isoelectric points of 5.1-5.2 and 4.0-4.2 and was free of interleukin-1, as determined by the absence of thymocyte-activating activity. FAF-M and other fibroblast-activating factors may contribute to wound healing and fibrosis in lesions characterized by mononuclear phagocyte infiltrates.