Induction of indoleamine 2,3-dioxygenase in alveolar interstitial cells of mouse lung by bacterial lipopolysaccharide.

Abstract

The cellular localization of indoleamine 2,3-dioxygenase was studied in the mouse lung after induction by lipopolysaccharide treatment. No significant indoleamine 2,3-dioxygenase activity was detected in alveolar macrophages and type II epithelial cells, which were recovered by alveolar lavages and trypsin-treatment, respectively. To determine this enzyme activity in other types of lung cells, we prepared monodispersed lung cells (6.5 X 10(7) cells/lung) by incubation with 0.1% collagenase and 0.1% trypsin. In a Percoll isopycnic gradient, the dispersed cells were distributed with two peaks at the densities of 1.040 and 1.080 g/ml. The enzyme activity was recovered exclusively in the lighter fractions. As examined by electron microscopy or more quantitatively by using various marker enzyme activities, endothelial cells (angiotensin-converting enzyme as a marker enzyme of these cells), alveolar interstitial cells (prostaglandin dehydrogenase), type I epithelial cells, type II epithelial cells, alveolar macrophages (beta-glucuronidase), Clara cells (coumarin hydroxylase), and polymorphonuclear leucocytes (arylsulfatase) were distributed with peaks at the densities of 1.033, 1.040, 1.042, 1.045, 1.070, 1.082, and 1.093 g/ml, respectively. The distribution pattern of the indoleamine 2,3-dioxygenase activity exactly coincided with that of alveolar interstitial cells. The localization of this enzyme in alveolar interstitial cells was immunohistochemically confirmed with the anti-indoleamine 2,3-dioxygenase antibody.