Alveolar macrophages from bronchoalveolar lavage of patients with pulmonary histiocytosis X: determination of phenotypic and functional changes.
In recent years the alveolar macrophage has been found to play a central role in interstitial lung disease. Pulmonary histiocytosis X is characterized by infiltrating fibroblasts, mononuclear cells, and CD-1-positive Langerhans cells. Bronchoalveolar lavage (BAL) fluid displays an increase of CD-1-positive cells and a remarkable exaggeration of the total cell count with only slight changes in the differential cell count. 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 pulmonary histiocytosis X was compared with that of 16 control patients. Immunophenotyping of alveolar macrophages by monoclonal maturation and differentiation markers of monocyte/macrophage lineage cells [Ki-M2, Ki-M6 (CD-68), Ki-M8, Ki-M1 (CD-11c)] revealed a significant increase of immature macrophages with a more monocyte-like phenotype. The proliferation marker Ki-67 revealed an increased proportion of proliferating macrophages. Functional analysis by measuring oxygen radical release revealed an increase both in baseline and stimulated luminol-enhanced chemiluminescence. Fibronectin production was elevated in alveolar macrophage supernatants from pulmonary histiocytosis X patients. These findings are consistent with phenotypic changes of alveolar macrophages in other interstitial lung diseases such as sarcoidosis and idiopathic pulmonary fibrosis. Local proliferation and the fresh influx of blood monocytes seem to be responsible for the increase in immature and functionally activated alveolar macrophages. The increase in oxygen radical release and fibronectin production suggests an augmented tissue injuring and fibrosing capacity of alveolar macrophages in pulmonary histiocytosis X.
Uebelhoer
M
M
I. Medizinische Klinik, Christian-Albrechts-Universität Kiel, Germany.
Bewig
B
B
Sternberg
K
K
Rabe
K
K
Nowak
D
D
Magnussen
H
H
Barth
J
J
D000328:Adult; D000911:Antibodies, Monoclonal; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D016022:Case-Control Studies; D005260:Female; D005353:Fibronectins / Q000096:biosynthesis; D005609:Free Radicals / Q000378:metabolism; D006646:Histiocytosis, Langerhans-Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D016676:Macrophages, Alveolar / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000378:metabolism; D010641:Phenotype
D000911:Antibodies, Monoclonal; D005353:Fibronectins; D005609:Free Radicals; D010100:Oxygen