Macrophages produce nitric oxide at allograft sites.
OBJECTIVE
The current study was designed to determine which cytokines produced during an alloimmune response stimulate macrophage nitric oxide (.N = O) production at allograft sites.


BACKGROUND
Previous work has demonstrated that rat sponge matrix allograft infiltrating cells produce more .N = O on stimulation with alloantigen than syngeneic graft-infiltrating cells. Addition of NG-monomethyl-L-arginine (NMA), an inhibitor of .N = O synthesis, promotes allospecific cytolytic T-lymphocyte effector function.


METHODS
Polyurethane sponges were implanted subcutaneously in recipient Lewis rats and injected with 10 x 10(6) ACl splenocytes. On various days after grafting, graft-infiltrating cells were harvested for in vitro study. Adherent macrophages from the graft infiltrating cell population were obtained by a 2- to 3-hour incubation to plastic dishes with subsequent washing to remove nonadherent cells.


RESULTS
Stimulation of unseparated graft-infiltrating cell populations with lipopolysaccharide or interferon-tau resulted in enhanced .N = O synthesis by allograft infiltrating cells compared with syngeneic graft-infiltrating cells, early after grafting. Macrophages recovered from an allograft site spontaneously produce more .N = O than macrophages recovered from syngeneic grafts (p < 0.001). Significantly enhanced levels of .N = O were produced by allograft macrophages compared with syngeneic graft macrophages on stimulation with lipopolysaccharide or interferon-tau (p < or = 0.025).


CONCLUSIONS
Nitric oxide appears to be produced in response to the local cytokines secreted by an ongoing rejection reaction. Nitric oxide serves under these circumstances to modulate the alloimmune response.
Langrehr
J M
JM
Department of Surgery, Free University Berlin, Germany.
White
D A
DA
Hoffman
R A
RA
Simmons
R L
RL
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000276:immunology*; D007370:Interferon Type I; D007371:Interferon-gamma / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D011257:Pregnancy Proteins; D051381:Rats; D011912:Rats, Inbred ACI; D011917:Rats, Inbred Lew; D014181:Transplantation Immunology / Q000502:physiology*; D014184:Transplantation, Homologous / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D007370:Interferon Type I; D007378:Interleukins; D008070:Lipopolysaccharides; D011257:Pregnancy Proteins; D014409:Tumor Necrosis Factor-alpha; C020947:interferon tau; D009569:Nitric Oxide; D007371:Interferon-gamma