Phenotypic and functional changes in alveolar macrophages contribute to the pathogenesis of pulmonary sarcoidosis

Bronchoalveolar lavage (BAL) was performed on 10 patients with sarcoidosis and 10 normal volunteers. In each case aliquots of the lavage were used to prepare cytospins on which differential cell counts were performed. Immunocytological methods using monoclonal antibodies RFD1 and RFD7 (identifying dendritic cells and mature macrophages in normal tissues) were performed to identify macrophage subsets. Sarcoid BAL contained a significantly higher proportion of RFD1+ cells (mean 44.7 +/- 10.32% compared to 12.3 +/- 4.0% in normals). Much of this increase was accounted for by a highly significant rise in the proportion of cells with the double phenotype RFD1+/RFD7+ (27.2 +/- 6.1% in sarcoid compared to 7.3 +/- 2.0% in normal). Suspensions of sarcoid and normal BAL were also studied in autologous mixed lymphocyte reactions (AMLR) using peripheral blood mononuclear cells (PBM) as a responder population. AMLRs were therefore set up using BAL, PBM, and BAL with PBM. In each case reactivity was compared to mitomycin treated controls. These studies revealed that sarcoid PBM expressed markedly reduced AMLR reactivity when compared to normal but both sarcoid and normal BAL were relatively unreactive. BAL admixed with PBM suppressed peripheral blood AMLR reactivity in the normals. In sarcoid patients BAL admixed with PBM abolished AMLR completely. We suggest that changes within the BAL macrophage populations in sarcoid patients may significantly influence the pathogenesis of this disease.