Alveolar macrophages in idiopathic pulmonary fibrosis display a more monocyte-like immunophenotype and an increased release of free oxygen radicals

Abstract

Bronchoalveolar lavage (BAL) was performed in 13 patients with idiopathic pulmonary fibrosis (IPF) and in 10 control subjects. Free oxygen radical (FOR) production of alveolar macrophages (AM) and of blood monocytes was measured by luminol-dependent chemiluminescence (LDCL) without and after stimulation with zymosan A. We confirmed earlier studies that alveolar macrophages of IPF patients display a significantly elevated release of FOR under basic and under stimulated conditions. In contrast to alveolar macrophages, blood monocytes did not reveal altered LDCL in IPF. This indicates that the functional properties for augmented FOR release by IPF alveolar macrophages are acquired in the lungs and not in the peripheral circulation. To elucidate the possible mechanisms leading to the augmented LDCL response, immunophenotyping of alveolar macrophages was carried out. A panel of new monoclonal antibodies of the Ki-M-series, discriminating differentiation stages of monocyte/macrophage subpopulations, served for immunocytochemical staining. In IPF patients distribution of Ki-M2, Ki-M3, Ki-M6 and Ki-M8 positive AM demonstrated an increased proportion of alveolar macrophages expressing a more monocyte-like immunophenotype. Normally, monocytes as precursors of AM reveal a markedly stronger LDCL than alveolar macrophages themselves. Therefore, it seems likely that the increased LDCL of alveolar macrophages in IPF is due to the higher proportion of more immature monocyte-like cells in the alveoli of these patients.