ALVEOLAR MACROPHAGES FROM BRONCHOALVEOLAR LAVAGE OF PATIENTS WITH PULMONARY HISTIOCYTOSIS .10. DETERMINATION OF PHENOTYPIC AND FUNCTIONAL-CHANGES

In recent years the alveolar macrophage has been found to play a centr al role in interstitial lung disease. Pulmonary histiocytosis X is cha racterized by infiltrating fibroblasts, mononuclear cells, and CD-1-po sitive Langerhans cells. Bronchoalveolar lavage (BAL) fluid displays a n increase of CD-1-positive cells and a remarkable exaggeration of the total cell count with only slight changes in the differential cell co unt. Changes of alveolar macrophage phenotype and functional activity occurring in pulmonary histiocytosis X have not yet been characterized . The BAL fluid of nine patients with histologically proven isolated p ulmonary histiocytosis X was compared with that of 16 control patients . Immunophenotyping of alveolar macrophages by monoclonal maturation a nd differentiation markers of monocyte/ macrophage lineage cells [Ki-M 2, Ki-M6 (CD-68), Ki-M8, Ki-M1 (CD-11c)] revealed a significant increa se of immature macrophages with a more monocyte-like phenotype. The pr oliferation marker Ki-67 revealed an increased proportion of prolifera ting macrophages. Functional analysis by measuring oxygen radical rele ase revealed an increase both in baseline and stimulated luminol-enhan ced chemiluminescence. Fibronectin production was elevated in alveolar macrophage supernatants from pulmonary histiocytosis X patients. Thes e findings are consistent with phenotypic changes of alveolar macropha ges in other interstitial lung diseases such as sarcoidosis and idiopa thic pulmonary fibrosis. Local proliferation and the fresh influx of b lood monocytes seem to be responsible for the increase in immature and functionally activated alveolar macrophages. The increase in oxygen r adical release and fibronectin production suggests an augmented tissue injuring and fibrosing capacity of alveolar macrophages in pulmonary histiocytosis X.