Synthesis of leukotriene C and other arachidonic acid metabolites by mouse pulmonary macrophages.

ABSTRACT

Mouse resident pulmonary macrophages were subdivided into alveolar (PAM) and interstitial (PTM) populations on the basis of accessibility to pulmonary lavage, and zymosan-induced arachidonic acid (204) metabolism was examined in both populations labeled with [3H]204. Maximal phagocytic doses of unopsonized zymosan induced the specific release of 11% of phospholipid 204 by PTM and 4.6% by PAM. Direct fatty acid analysis of [3H]204-labeled PTM cultured in the presence or absence of zymosan indicated that the specific activity of the [3H]204 in cell phospholipid provided an accurate measure of 204 released by the cells, and could therefore be used to quantitate the synthesis of 204 metabolites by PTM in vitro. The single major 204 metabolite of PTM was the slow-reacting substance leukotriene C, which was synthesized in quantities of 3-4 pmol/microgram cell protein (280-370 pmol/10(6) cells), and comprised 20-25% of the released 204. PTM also synthesized prostaglandin E2, prostacyclin, thromboxane A2, and hydroxyeicosatetraenoic acids. In contrast, PAM produced leukotrienes D and E in addition to leukotriene C, prostaglandin E2, thromboxane A2, and hydroxyeicosatetraenoic acids. Prostacyclin formation by PAM was not observed. These studies define a set of experimental conditions for the study of 204 metabolism by pulmonary macrophages, and demonstrate that these cells are rich sources of LTC as well as other 204 oxygenated products.