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The Substance P Receptor Is Necessary for a Normal Granulomatous Response in Murine Schistosomiasis Mansoni

1999; American Association of Immunologists; Volume: 162; Issue: 10 Linguagem: Inglês

10.4049/jimmunol.162.10.6080

1550-6606

Arthur Blum, Ahmed Metwali, Mindy Kim-Miller, Jie Li, Khurram Qadir, David E. Elliott, Bao Lu, Zsuzsa Fábry, Norma P. Gerard, Joel V. Weinstock,

Vitamin K Research Studies

Abstract Immune cells within the granulomas of murine schistosomiasis mansoni make the neuropeptide substance P (SP) and express neurokine 1 receptor, which is the specific receptor for substance P (SPr). It was determined if mice with deletion of the SPr (SPr−/−) would develop a normal granulomatous response to schistosome ova during the course of natural infection. Mean liver granuloma size was smaller in SPr−/− mice compared with that of wild-type control animals. Although flow analysis revealed little difference in the cellular composition of the granulomas, both splenocytes and granuloma cells from SPr−/− mice produced much less IFN-γ and IgG2a and less IgE. The expression of Th2 cytokines (IL-4/IL-5) and IgG1 was comparable to the wild-type control. The mouse with targeted disruption of its SPr had the nonmammalian gene encoding the enzyme β-galactosidase inserted in exon 1 of the SPr gene. There was β-galactosidase activity in many mononuclear cells scattered throughout the schistosome granulomas of SPr−/− mice. Also, a granuloma T cell line derived from this transgenic mouse produced β-galactosidase. These results provide further evidence that in murine schistosomiasis SPr is displayed commonly on granuloma inflammatory cells and is important for granuloma development and expression of IFN-γ circuitry in this natural infection.