Generation of xenopsin-related peptides from tissue precursors by media conditioned by endotoxin-stimulated rat peritoneal macrophages.

Incubation of media conditioned by endotoxin-stimulated rat peritoneal macrophages generates immunoreactive xenopsin (iXP) when incubated with acid extracts of various tissues of the rat. The generation of iXP, as measured by specific radioimmunoassay and confirmed by HPLC analysis, increased as the length of the incubation period increased and was inhibited by pepstatin, prior boiling of the conditioned media, or by omitting either the tissue extract or the conditioned media. The pH optimum for the generation of iXP was 3.0. The generated iXP showed biological activity in that stimulated histamine secretion from isolated rat mast cells and this secretory response was prevented by metabolically poisoning the cells. In addition, the generated iXP stimulated contraction of the isolated guinea pig ileum. In this regard, it was similar to neurotensin (NT). Tissue precursor levels for iXP, as measured by this system of generation, were highest in kidney, liver, and skin and lowest in skeletal muscle and plasma. These results suggest to us that during the inflammatory response, the NT-related peptide, xenopsin, can be generated from tissue precursor(s) by enzymes secreted by invading macrophages. The generated XP may then affect the participating cells of inflammation.