Leukotriene B4 production by the human alveolar macrophage: a potential mechanism for amplifying inflammation in the lung.

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 LTB4 in lung inflammatory responses, we investigated the production of LTB4 by human alveolar macrophages and determined its chemotactic activity for lung and blood phagocytes in vitro and in vivo. Human alveolar macrophages were stimulated with the calcium ionophore A23187 (10 micrograms/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/10(6) cells) and 3 of 4 smokers (23.4 +/- 14.8 ng/10(6) 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 less than 0.05). When instilled into the airways of anesthetized rats, LTB4 was less potent as an attractant for neutrophils and mononuclear cells than either 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.