Granuloma T lymphocytes in murine schistosomiasis mansoni have somatostatin receptors and respond to somatostatin with decreased IFN-gamma secretion.
The granulomas of mice infected with Schistosoma mansoni for 8 wk have macrophages that secrete somatostatin 1-14 (SOM). Within the granuloma, SOM has no known function. To uncover the possible significance of SOM produced within this granulomatous inflammation, we sought SOM receptors on distinct cellular components of the granuloma to identify cells targeted for SOM action. [125I]SOM 1-14 bound to dispersed granuloma inflammatory cells specifically and reversibly. Scatchard analysis suggested one receptor type (kDa 4.28 x 10(-9) M). Octreotide, a stable SOM derivative, displaced radioligand (kDa 1.01 x 10(-10) M), but SOM 1-28, substance P, and vasoactive intestinal peptide did not. The SOM receptor localized exclusively to a subset of granuloma CD4+ T lymphocytes. Using IL-5 and IFN-gamma ELISA, it was shown that granuloma T cells can secrete appreciable IL-5 and IFN-gamma when stimulated with Ag or mitogen. Both SOM and octreotide at concentrations as low as 10(-10) M substantially decreased IFN-gamma secretion from Ag or mitogen-stimulated T cells, but at concentrations as high as 10(-6) did not affect IL-5 production. Octreotide administered to animals in vivo decreased the intensity of the granulomatous response. Thus, some granuloma T cells have SOM 1-14 receptors. SOM 1-14, a product of granuloma macrophages, may participate in regulation of the granulomatous response by modulating the secretion of some lymphokines. Octreotide, a clinically useful SOM analog, mimics the action of SOM on the immune system.
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.
A M
AM
Blum
A
A
Metwali
R C
RC
Mathew
G
G
Cook
D
D
Elliott
J V
JV
Weinstock
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D006099:Granuloma / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism*; D008222:Lymphokines / Q000096:biosynthesis; D051379:Mice; D008808:Mice, Inbred CBA; D015282:Octreotide / Q000494:pharmacology; D017481:Receptors, Somatostatin / Q000378:metabolism*; D012555:Schistosomiasis mansoni / Q000276:immunology*; D013004:Somatostatin / Q000494:pharmacology*
D008222:Lymphokines; D017481:Receptors, Somatostatin; D013004:Somatostatin; D007371:Interferon-gamma; D015282:Octreotide