PROLIFERATION OF MATURE AND IMMATURE SUBPOPULATIONS OF BRONCHOALVEOLAR MONOCYTES MACROPHAGES AND PERIPHERAL-BLOOD MONOCYTES

A continuous influx of peripheral blood monocytes (PBM) to the lung is thought to maintain the local population of alveolar macrophages (AM) . However, local proliferation of a small subpopulation of AM has been demonstrated in animal studies and in humans. AM exhibit a great hete rogeneity with regard to their morphology (cell size, shape of nucleus ), immunophenotype (expression of CD14 and RFD9 antigen), and function . Part of this heterogeneity may be explained by the presence of diffe rent maturation stages of AM, ranging from small immature, CD14(+) RFD 9(-) PBM-like cells to large, CD14(-) RFD9(+) mature AM. These finding s prompted us to study whether proliferation of PBM and AM is related to their stage of maturation. The expression of the proliferation mark er Ki-67 was studied in AM from both healthy volunteers and patients s uffering from sarcoidosis. Using double immuno-fluorescence staining, we studied proliferation of immature, CD14(+) AM, and mature, RFD9(+) AM in sarcoidosis, and we compared this with PBM. A significantly larg er percentage of AM in general expressed Ki-67 antigen in sarcoidosis (3.0 (median); range 1.1-5.5) as compared with healthy volunteers (0.8 ; 0.2-1.3). In sarcoidosis, proliferation was observed in both the imm ature and the mature subpopulation of AM. Proliferating PBM were rarel y observed [less than 0.2% of the CD14(+) mononuclear cells (MNC)] bot h in healthy volunteers and sarcoidosis patients. A small subpopulatio n of PBM showed a weak expression of RFD9 antigen (less than 1% of MNC ). Interestingly, proliferation of PBM was concentrated in this subpop ulation (15% of the RFD9(+) MNC). These data show that even mature AM, which are generally thought to be terminally differentiated cells wit h little capacity to replicate, are able to proliferate, whereas a rel atively very low percentage of their precursors in the blood circulati on proliferates. Furthermore, the findings suggest that lung tissue in sarcoidosis creates an environment which promotes proliferation of mo nocytic cells.