LEUKOTRIENE-B4 PRODUCTION BY THE HUMAN ALVEOLAR MACROPHAGE - A POTENTIAL MECHANISM FOR AMPLIFYING INFLAMMATION IN THE LUNG

Publisher Website
Google Scholar
Abstract
Leukotriene B4 (LTB4) is a lipoxygenase product of arachidonic acid that has potent chemotactic activity for blood leukocytes. To assess the potential role of LTB, in lung inflammatory responses, production of LTB4 by human alveolar macrophages was investigated and its chemotactic activity for lung and blood phagocytes was determined in vitro and in vivo. Human alveolar macrophages were stimulated with the calcium ionophore A23187 (10 .mu.g/ml), and lipoxygenase products in the supernatants were isolated by high-performance liquid chromatography. Leukotriene B4 was the predominant arachidonate lipoxygenase product from the alveolar macrophages of 2 nonsmokers (17.3 .+-. 2.7 ng/106 cells) and 3 of 4 smokers (23.4 .+-. 14.8 ng/106 cells). Alveolar macrophages produced more LTB4 than did similarly treated peripheral blood neutrophils. Stimulated alveolar macrophages also produced 5-hydroxyeicosatetraenoic acid (HETE) and 2 isomers of LTB4:5-(S),12-(R)-6-trans-LTB4 and 5-(S),12-(S)-6-trans-LTB4. Leukotriene B4 showed little chemotactic activity for alveolar macrophages in vitro and was a more potent chemoattractant for peripheral blood neutrophils than for monocytes (P < 0.05). When instilled into the airways of anesthetized rats, LTB4 was less potent as an attractant for neutrophils and mononuclear cells than zymosan-activated serum or bacterial-derived chemotactic factors. Leukotriene B4 production by alveolar macrophages may provide a mechanism by which phagocytes are recruited to the human lung during inflammatory processes.