The substance P receptor is necessary for a normal granulomatous response in murine schistosomiasis mansoni

Arthur M Blum; Ahmed Metwali; Mindy Kim-Miller; Jie Li; Khurram Qadir; David E Elliott; Bao Lu; Zsuzsa Fabry; Norma Gerard; Joel V Weinstock

doi:10.4049/jimmunol.162.10.6080

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The substance P receptor is necessary for a normal granulomatous response in murine schistosomiasis mansoni

Journal article

Peer reviewed

The substance P receptor is necessary for a normal granulomatous response in murine schistosomiasis mansoni

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

The Journal of immunology (1950), Vol.162(10), pp.6080-6085

05/15/1999

DOI: 10.4049/jimmunol.162.10.6080

PMID: 10229849

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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-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.

RNA, Messenger - isolation & purification

Schistosomiasis mansoni - immunology

Cytokines - analysis

Immunoglobulin E - biosynthesis

Mice, Inbred C57BL

Th2 Cells - immunology

Granuloma - pathology

Immunoglobulin Isotypes - biosynthesis

Liver - immunology

Animals

B-Lymphocytes - immunology

Immunoglobulin G - biosynthesis

Mice, Mutant Strains

Granuloma - immunology

Receptors, Neurokinin-1 - metabolism

Mice

Liver - parasitology

Receptors, Neurokinin-1 - genetics

Genes, Reporter

Granuloma - etiology

Interferon-gamma - biosynthesis

Details

Title: Subtitle: The substance P receptor is necessary for a normal granulomatous response in murine schistosomiasis mansoni
Creators: Arthur M Blum - Division of Gastroenterology-Hepatology, Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA
Ahmed Metwali
Mindy Kim-Miller
Jie Li
Khurram Qadir
David E Elliott
Bao Lu
Zsuzsa Fabry
Norma Gerard
Joel V Weinstock
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.162(10), pp.6080-6085
DOI: 10.4049/jimmunol.162.10.6080
PMID: 10229849
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Grant note: DK38327 / NIDDK NIH HHS DK25295 / NIDDK NIH HHS DK02428 / NIDDK NIH HHS
Language: English
Date published: 05/15/1999
Academic Unit: Gastroenterology and Hepatology; Internal Medicine
Record Identifier: 9984094579702771

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