Isolated hepatic granulomas from mice infected with Schistosoma mansoni contain nerve growth factor

Abstract

Nerve growth factor (NGF) is a neurotrophic factor essential for the development and maintenance of specific neuronal cell populations. In addition, NGF has biological effects on inflammatory cells. The aim of this study was to determine whether NGF is present in chronic inflammation, using isolated hepatic granulomas from mice infected with Schistosoma mansoni as the model. The schistosome granuloma is a complex T-cell-mediated immune response to the egg. Intact granulomas were isolated from the livers of infected mice and examined for the presence of NGF. In homogenized granuloma samples, radioimmunoassay and immunoblotting analyses detected an immunoreactive NGF that had the same molecular mass as that of purified murine NGF (13 kDa). Isolated granulomas cultured in vitro released soluble factor(s) with NGF-like neurite-promoting activity in a rat pheochromocytoma (PC12) bioassay. This activity was partially inhibited by a blocking anti-NGF antibody. There were two potential sources of this NGF-like neurite-promoting activity, either the schistosome egg or the host inflammatory response. Since neither isolated eggs nor soluble egg antigen had neurite-promoting activity, the inflammation was the source of this activity. The inability of the anti-NGF antibody to inhibit completely the granuloma-induced neurite outgrowth in the bioassay signifies that NGF is not the only neurotrophic factor present in these granulomas. The presence of NGF within the granulomas may indicate that NGF has a role in the granulomatous response.