Effects of granuloma modulation induced by regulatory-T-lymphocyte activity on angiotensin II/III production by granuloma macrophages in murine schistosomiasis mansoni.
Angiotensins are produced by granuloma macrophages in murine Schistosoma mansoni. During the course of infection, granuloma undergo a T-cell-dependent process called modulation in which their maximal size decreases. This study was undertaken to establish whether angiotensin production by granuloma macrophages is altered by immunoregulatory lymphocytes. Granuloma macrophages from modulated lesions released and contained more angiotensin II/III (AII/III) and less angiotensin I (AI) than those from the acute infection. Captopril, a specific angiotensin-converting-enzyme (ACE) inhibitor, appreciably decreased AII/III produced by macrophages from modulated granulomas. Adoptive transfer of splenic T lymphocytes from chronically infected donors into acutely infected recipients altered angiotensin production by the granuloma macrophages in a manner similar to that seen in modulated lesions. However, no difference was detected in the capacity of granuloma macrophages from acutely or chronically infected mice to metabolize 125I-AI or -AII added to cell cultures. Similarly, captopril did not alter the metabolism of exogenously administrated angiotensins. These findings suggest that regulatory T lymphocytes influence the metabolism by granuloma macrophages of endogenously produced angiotensins at least in part by induction of macrophage ACE activity. However, the degradation of extracellular AI and AII may result from the activity of enzymes other than ACE which are not inducible by modulation.
Weinstock
J V
JV
Blum
A M
AM
D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000096:biosynthesis*; D000805:Angiotensin III / Q000096:biosynthesis*; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006099:Granuloma / Q000276:immunology* / Q000469:parasitology; D007106:Immune Sera / Q000276:immunology; D008107:Liver Diseases / Q000276:immunology / Q000469:parasitology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008808:Mice, Inbred CBA; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D012550:Schistosoma mansoni; D012552:Schistosomiasis / Q000276:immunology*; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D007106:Immune Sera; D000804:Angiotensin II; D000805:Angiotensin III; D002216:Captopril; D007703:Peptidyl-Dipeptidase A