Substance P modulates antigen-induced, IFN-γ production in murine Schistosomiasis mansoni

Arthur M Blum; AHMED Metwali; George Cook; Ranjit C Mathew; David Elliott; Joel V Weinstock

doi:10.4049/jimmunol.151.1.225

Back

Substance P modulates antigen-induced, IFN-γ production in murine Schistosomiasis mansoni

Journal article

Peer reviewed

Substance P modulates antigen-induced, IFN-γ production in murine Schistosomiasis mansoni

Arthur M Blum, AHMED Metwali, George Cook, Ranjit C Mathew, David Elliott and Joel V Weinstock

The Journal of immunology (1950), Vol.151(1), pp.225-233

1993

DOI: 10.4049/jimmunol.151.1.225

PMID: 7686934

View Online

Abstract

In murine Schistosomiasis mansoni, granuloma eosinophils make SP. We investigated whether SP affects lymphokine secretion in murine schistosomiasis. SP at > or = 10(-10) M, and other tachykinins at much higher concentrations, substantially increased IFN-gamma secretion from spleen or granuloma inflammatory cells primed in vitro by suboptimal stimulatory concentrations of egg Ag or mitogen. Cells receiving maximal antigenic or mitogenic stimulation were affected marginally. Also, tachykinins induced no IFN-gamma from resting cells receiving no Ag or mitogen stimulation. There are three distinct tachykinin receptors, called NK-1, NK-2 and NK-3. SP binds the NK-1 receptor with highest affinity. Specific NK-1 receptor antagonists blocked all tachykinin-induced, IFN-gamma secretion. An NK-2 receptor inhibitor had no effect. Thus, SP and other tachykinins were acting through an NK-1 receptor. Inflammatory cells from 4-day-old granulomas cultured in vitro secrete IFN-gamma. Yet, there was no measurable IFN-gamma when SP receptor antagonists were added to the cultures. Moreover, animals treated in vivo with the NK-1 receptor antagonist CP-96,345 produced smaller granulomas. This suggested that endogenous SP may be necessary for normal induction of granuloma IFN-gamma secretion and a normal granulomatous response. Granuloma macrophages make somatostatin (SOM) that can decrease IFN-gamma secretion. Yet, IFN-gamma secretion was unaffected when both SP and SOM were in the cell cultures. In conclusion, SP modulates Ag-driven IFN-gamma secretion through a NK-1 receptor. Also, SP and SOM may be components of a natural circuit within inflammation that regulates IFN-gamma production.

Infectious Diseases

Biological and medical sciences

Diseases caused by trematodes

Helminthic diseases

Medical sciences

Parasitic diseases

Schistosomiases

Details

Title: Subtitle: Substance P modulates antigen-induced, IFN-γ production in murine Schistosomiasis mansoni
Creators: Arthur M Blum - University of Iowa
AHMED Metwali - University of Iowa
George Cook - University of Iowa
Ranjit C Mathew - Univ. Iowa coll. medicine, dep. internal medicine, div. gastroenterology-hepatology, Iowa City IA 52242, United States
David Elliott - Univ. Iowa coll. medicine, dep. internal medicine, div. gastroenterology-hepatology, Iowa City IA 52242, United States
Joel V Weinstock - Univ. Iowa coll. medicine, dep. internal medicine, div. gastroenterology-hepatology, Iowa City IA 52242, United States
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.151(1), pp.225-233
DOI: 10.4049/jimmunol.151.1.225
PMID: 7686934
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Publisher: American Association of Immunologists
Language: English
Date published: 1993
Academic Unit: Gastroenterology and Hepatology; Internal Medicine
Record Identifier: 9984359764302771

Metrics

11 Record Views

65 Times Cited - Web of Science