The distribution of phenotypically distinct macrophage subsets in the lungs of patients with cryptogenic fibrosing alveolitis

Abstract

Monoclonal antibodies that identify phenotypically distinct macrophage subsets were used to analyse the macrophages in lung biopsy specimens and bronchoalveolar lavage fluid from patients with cryptogenic fibrosing alveolitis. Among the antibodies were RFD1, an interdigitating cell marker, RFD7, a marker for mature tissue macrophages, and RFD9, which identifies epithelioid cells as well as germinal centre macrophages. The lavage fluid was found to contain abnormally high numbers of cells staining with each of the antibodies, a finding that could be explained, at least in part, by an increased frequency of cells expressing more than one marker. In lung tissue macrophage phenotypes within the interstitium were found to differ significantly from those in the alveolar space. Most strikingly, cells bearing the antigen recognized by RFD9 were entirely absent from the interstitial macrophage population, whereas the vast majority in the alveolar lumen were RFD9-positive. The discrete compartmentalization of phenotypically different macrophages within the lung suggests that macrophages may contribute differently to lung pathology in each microenvironment. The functional capacity of the unusual RFD9-positive alveolar macrophages remains to be determined, but their close association with the process of alveolar occlusion indicates a role in the fibrotic process.