The biosynthesis of leukotriene B4, the predominant lipoxygenase product in rabbit alveolar macrophages, is enhanced during immune activation.
Rabbit alveolar macrophages synthesize prostaglandins in response to various stimuli. We have previously shown that prostaglandin production was decreased in immunologically activated (live Bacillus Calmette-Guérin (BCG)-injected) animals. (Hsueh, W., Lamb, R. and Gonzalez-Crussi, F. (1982) Biochim. Biophys. Acta 710, 406-414). In the present study, we examined the lipoxygenase products of alveolar macrophages from normal and immunologically activated rabbits injected intravenously with live BCG or complete Freund's adjuvant. We found: unstimulated lung macrophages produced no detectable leukotrienes; the predominant lipoxygenase product upon stimulation was leukotriene B4; alveolar macrophages did not significantly degrade leukotriene B4 into its 20-hydroxy derivative, and the total degradation of leukotriene B4 during 90 min of incubation was minimal; the production of leukotriene B4 reached the peak at 30 min after A23187 stimulation, while zymosan caused a much slower and smaller release; following stimulation, immunologically activated lung macrophages produced more leukotriene B4 than resident macrophages. It is possible that the increased leukotriene B4 production in immunologically activated lung macrophages was related to the immunoregulatory function of this substance, such as enhancing cytotoxicity, interferon production and proliferation of suppressor-cytotoxic T cells.
Hsueh
W
W
Sun
F F
FF
Henderson
S
S
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D007114:Immunization; D007975:Leukotriene B4 / Q000096:biosynthesis*; D008084:Lipoxygenase / Q000378:metabolism*; D008262:Macrophage Activation; D008264:Macrophages / Q000201:enzymology*; D008297:Male; D011650:Pulmonary Alveoli / Q000276:immunology*; D011817:Rabbits; D013997:Time Factors
D007975:Leukotriene B4; D000001:Calcimycin; D008084:Lipoxygenase; D002118:Calcium