Bystander injury of host lymphoid tissue during murine graft-verus-host disease is mediated by nitric oxide.
The suppressed lymphocyte proliferative responses characteristic of graft-versus-host disease (GVHD) are due, in part, to production of nitric oxide (NO). In order to more fully elucidate the role of NO during GVHD, an NO synthesis inhibitor, aminoguanidine (AG), was administered to unirradiated (C57BL/6J X DBA/2J)F1 mice injected with 5 X 10(7) C57BL/6J splenocytes. Administration of AG resulTed in abrogation of the elevation in serum NO2- + NO3- levels characteristic of GVHD. A significantly increased percentage of splenocytes of host phenotype (H2b/d, B220+, and THY1.2+) and a significantly higher hematocrit value were detected in GVHD animals receiving AG therapy. Additionally, the Con A-induced proliferative response of splenocytes obtained from GVHD mice receiving AG therapy was increased compared with the responses of splenocytes from animals that did not receive AG therapy. Parameters not affected by AG therapy included NO synthesis by recovered peritoneal macrophages, donor antihost cytolytic activity in splenocyte populations, serum GM-CSF levels and long-term engraftment of donor cells. These data indicate that NO may play a role in the destruction of both lymphoid and erythroid host tissue as well as the reduced lymphoproliferative responses associated with the acute phase of GVHD.
Hoffman
R A
RA
Department of Surgery, University of Pittsburgh, Pennsylvania 15261, USA.
Langrehr
J M
JM
Berry
L M
LM
White
D A
DA
Schattenfroh
N C
NC
McCarthy
S A
SA
Simmons
R L
RL
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D017690:Cell Transplantation; D003602:Cytotoxicity, Immunologic; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood; D006146:Guanidines / Q000494:pharmacology; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D009573:Nitrites / Q000097:blood; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology
D004791:Enzyme Inhibitors; D006146:Guanidines; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C004479:pimagedine