Effects of mononuclear cells on pulmonary arteries from rejecting transplanted lungs.
Experiments were designed to determine responses of pulmonary arteries from an acutely rejecting, transplanted lung to rejection-activated mononuclear cells. Pulmonary arteries and macrophage-depleted mononuclear cells were obtained from unoperated dogs (control) and dogs with rejecting single lung allotransplants (transplanted, rejecting). In some arteries, the endothelium was removed deliberately. Pulmonary arteries were suspended for measurement of isometric force in organ chambers. Contractions to potassium chloride (60 M) were greater in rings of pulmonary arteries from rejecting compared with control dogs. Mononuclear cells from both control and transplanted dogs caused cell number-dependent contractions of autogenous pulmonary arteries. Contractions to cells were decreased when the endothelium was present only in arteries from control dogs; these contractions were increased by the L-arginine analog N(G)-monomethyl-L-arginine (10(-4) M) but not by indomethacin (10(-5) M). Contractions to mononuclear cells were reduced by superoxide dismutase (150 U/ml) and catalase (1,200 U/ml) in arteries without endothelium from control but not transplanted dogs. In arteries from transplanted dogs, contractions to mononuclear cells were reduced by desferoxamine (10(-3) M). Results suggest that interactions between mononuclear cells and pulmonary arteries are modified during rejection of lung allografts so that, during rejection, 1) endothelium-derived nitric oxide no longer antagonizes contractions to substances produced by the mononuclear cells and 2) contractions of smooth muscle from rejecting arteries to mononuclear cells may be mediated by radicals other than superoxide.
Wiklund
L
L
Department of Physiology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Miller
V M
VM
Tazelaar
H D
HD
McGregor
C G
CG
D000208:Acute Disease; D000818:Animals; D004285:Dogs; D006084:Graft Rejection / Q000503:physiopathology*; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D016040:Lung Transplantation / Q000276:immunology*; D008297:Male; D008855:Microscopy, Electron, Scanning; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology; D011651:Pulmonary Artery / Q000473:pathology / Q000503:physiopathology*