Effects of mononuclear cells on pulmonary arteries from rejecting,
transplanted lungs.
Wiklund, Lars, Virginia M. Miller, Henry D. Tazelaar, Christopher G.
A. McGregor.
Division of Thoracic and Cardiovascular Surgery, Departments of
Physiology and Biophysics and Pathology, Mayo Clinic and Foundation,
Rochester, Minnesota
APStracts 3:0190L, 1996.
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 mol/L) were greater in rings of pulmonary arteries from rejecting
compared to 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, L-NMMA
(10-4mol/L), but not by indomethacin (10-5mol/L). Contractions to
mononuclear cells were reduced by superoxide dismutase (150U/mL) and
catalase (1200U/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
-3mol/L). 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.
Received 3 June 1996; accepted in final form 15 October 1996.
APS Manuscript Number L161-6.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 13 November 1996