title: 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 (20:4) metabolism was examined in both populations labeled with [3H]20:4. Maximal phagocytic doses of unopsonized zymosan induced the specific release of 11% of phospholipid 20:4 by PTM and 4.6% by PAM. Direct fatty acid analysis of [3H]20:4-labeled PTM cultured in the presence or absence of zymosan indicated that the specific activity of the [3H]20:4 in cell phospholipid provided an accurate measure of 20:4 released by the cells, and could therefore be used to quantitate the synthesis of 20:4 metabolites by PTM in vitro. The single major 20:4 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 20:4. 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 20:4 metabolism by pulmonary macrophages, and demonstrate that these cells are rich sources of LTC as well as other 20:4 oxygenated products.
mesh_terms: D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D050356:Lipid Metabolism; D008168:Lung / Q000166:cytology*; D008264:Macrophages / Q000145:classification / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010587:Phagocytosis; D010743:Phospholipids / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000166:cytology; D013189:SRS-A / Q000096:biosynthesis*; D015054:Zymosan / Q000494:pharmacology; D005723:gamma-Glutamyltransferase / Q000378:metabolism
chemical_list: D001095:Arachidonic Acids; D010743:Phospholipids; D013189:SRS-A; D016718:Arachidonic Acid; D015054:Zymosan; D005723:gamma-Glutamyltransferase