Granulomas in murine schistosomiasis mansoni contain vasoactive intestinal peptide-responsive lymphocytes.
Granulomas develop around schistosome ova in murine Schistosoma mansoni. These granulomas have eosinophils that produce VIP. It is possible that VIP participates in immunoregulation. VIP-mediated effects usually operate through a cAMP-dependent mechanism. To identify VIP-responsive inflammatory cells in murine schistosomiasis, inflammatory cells were exposed to VIP and assessed for adenylate cyclase activation and VIP binding. VIP increased adenylate cyclase activity in splenic lymphocytes from both normal and infected mice. In each case, the half-maximal stimulation was at about 5 x 10(-8) M. [125I]VIP bound to splenic lymphocytes specifically, with a Kd of 10(-8) M. This suggested that maximal adenylate cyclase activation requires full receptor occupancy. The receptor was highly specific for VIP. Hormone analogs, that are VIP receptor antagonists in some tissues, were only weak agonists of the lymphocyte VIP receptor. Granuloma cells also bound VIP and responded with adenylate cyclase activation in a manner similar to that of spleen cells. Both splenic T and B lymphocytes responded to VIP. Deletion experiments, using anti-Thy 1.2, suggested that most of the responsive granuloma cells were T lymphocytes. Thus, VIP alters cAMP metabolism in granuloma T cells through a receptor-coupled mechanism similar to that observed for spleen cells. Binding studies on mouse intestinal epithelial cells suggested that their VIP receptor is functionally and possibly structurally different from the VIP receptor on mouse lymphocytes. Additional experiments suggested that VIP and other neuropeptides are unlikely to alter the granulomatous response through a primary interaction with the granuloma macrophages.
Department of Internal Medicine, University of Iowa, Iowa City 52242.
J V
JV
Weinstock
A M
AM
Blum
S
S
Khetarpal
D000262:Adenylyl Cyclases / Q000032:analysis; D000818:Animals; D004789:Enzyme Activation; D005260:Female; D006099:Granuloma / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008808:Mice, Inbred CBA; D010587:Phagocytosis / Q000187:drug effects; D011964:Receptors, Gastrointestinal Hormone / Q000032:analysis / Q000187:drug effects; D018005:Receptors, Vasoactive Intestinal Peptide; D012555:Schistosomiasis mansoni / Q000276:immunology*; D013004:Somatostatin / Q000494:pharmacology; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects*; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism / Q000494:pharmacology*
D011964:Receptors, Gastrointestinal Hormone; D018005:Receptors, Vasoactive Intestinal Peptide; D014660:Vasoactive Intestinal Peptide; D013004:Somatostatin; D000262:Adenylyl Cyclases