The substance P receptor is necessary for a normal granulomatous response in murine schistosomiasis mansoni.
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-gamma 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 beta-galactosidase inserted in exon 1 of the SPr gene. There was beta-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 beta-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-gamma circuitry in this natural infection.
Blum
A M
AM
Division of Gastroenterology-Hepatology, Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA.
Metwali
A
A
Kim-Miller
M
M
Li
J
J
Qadir
K
K
Elliott
D E
DE
Lu
B
B
Fabry
Z
Z
Gerard
N
N
Weinstock
J V
JV
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000032:analysis; D017930:Genes, Reporter; D006099:Granuloma / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D008099:Liver / Q000276:immunology / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D012333:RNA, Messenger / Q000302:isolation & purification; D018040:Receptors, Neurokinin-1 / Q000235:genetics / Q000378:metabolism*; D012555:Schistosomiasis mansoni / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
D016207:Cytokines; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1; D007073:Immunoglobulin E; D007371:Interferon-gamma