REDUCTION IN LEUKOTRIENE B-4 GENERATION BY BRONCHOALVELOAR LAVAGE CELLS IN ASTHMA

Background - Leukotrienes are inflammatory mediators implicated in the pathogenesis of asthma. The capacity of inflammatory cells within the airways to generate leukotrienes may be altered in asthma. This hypot hesis was tested using bronchoalveolar lavage (BAL) to sample cells wi thin the airways from atopic asthmatic and normal subjects, and by mea suring their capacity to generate leukotriene B-4 (LTB(4)) and leukotr iene C-4 (LTC(4)) in response to A23187, a potent stimulus of leukotri ene generation. Methods - Bronchoalveolar lavage was performed in 12 m ild asymptomatic atopic asthmatic patients and 12 normal subjects. Mix ed BAL cell aliquots (approximately 80% alveolar macrophages) were inc ubated with 0-20 mu M A23187 for 10 minutes and with 4 mu M A23187 for 0-30 minutes, and leukotrienes were measured by radioimmunoassay and high performance liquid chromatography. Results - Mixed BAL cells from asthmatic subjects generated less LTB(4) than cells from normal subje cts in dose response and time course experiments (area under the curve 81.5 (0.0-228.5) ng.min 10(-6) cells in asthmatic subjects and 197.9 (13.9-935.6) ng min 10(-6) cells in normal subjects. There were no dif ferences in LTC(4) generation between BAL cells from asthmatic and nor mal subjects. Conclusions - Generation of LTB(4) by BAL cells from ato pic asthmatic subjects in response to A23187 was reduced. As the alveo lar macrophage is the major source of LTB(4) in BAL cells, these resul ts probably reflect reduced generation of LTB(4) by alveolar macrophag es from asthmatic patients. This may be a consequence of monocyte migr ation into the lung, or altered alveolar macrophage function in asthma , or both.