Identification of the mouse calcium-binding proteins, MRP 8 and MRP 14, in Schistosoma mansoni-induced granulomas: biochemical and functional characterization.

Granuloma initiation factor (GIF), which elicits a granulomatous reaction in naive murine skin, contains low-molecular-weight proteins partially purified from organized granulomas developed in livers of mice with schistosomiasis. In this study, we found that 10- and 14-kDa proteins in the GIF are highly homologous to mouse migration inhibitory factor-related protein (MRP) 8 and MRP 14. Compared with the N-terminal amino acid sequence deduced from each corresponding cDNA, the 10-kDa protein from the granuloma lacks the first methionine, whereas the 14 kDa misses methionine, alanine, and asparagine. Immunohistochemically, cells expressing MRP 8 and MRP 14 considerably increased in different murine tissues after Schistosoma mansoni infection and concentrated in liver around the dilated blood vessels and at the edge of granulomas. The staining of differentiated macrophages and epithelioid cells located in the center of the granulomas was negative. Immunoreactivity of peritoneal exudate cells also was found to gradually disappear with time in cell culture. Furthermore, in vivo effects of the recombinant proteins in murine skin were described histologically. Both MRPs caused severe infiltration of neutrophils and monocytes during 7-14 days. The reaction resulting from individual MRP implantation became minimal after 50 days but inoculation of the Ca2+-dependent heterodimers showed an extensive eosinophil accumulation.