Proliferation of mature and immature subpopulations of bronchoalveolar monocytes/macrophages and peripheral blood monocytes.

Abstract

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 heterogeneity 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 different maturation stages of AM, ranging from small immature, CD14+ RFD9- PBM-like cells to large, CD14- RFD9+ mature AM. These findings prompted us to study whether proliferation of PBM and AM is related to their stage of maturation. The expression of the proliferation marker Ki-67 was studied in AM from both healthy volunteers and patients suffering from sarcoidosis. Using double immunofluorescence staining, we studied proliferation of immature, CD14+ AM, and mature, RFD9+ AM in sarcoidosis, and we compared this with PBM. A significantly larger 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 immature and the mature subpopulation of AM. Proliferating PBM were rarely observed [less than 0.2% of the CD14+ mononuclear cells (MNC)] both in healthy volunteers and sarcoidosis patients. A small subpopulation of PBM showed a weak expression of RFD9 antigen (less than 1% of MNC). Interestingly, proliferation of PBM was concentrated in this subpopulation (15% of the RFD9+ MNC). These data show that even mature AM, which are generally thought to be terminally differentiated cells with little capacity to replicate, are able to proliferate, whereas a relatively very low percentage of their precursors in the blood circulation proliferates. Furthermore, the findings suggest that lung tissue in sarcoidosis creates an environment which promotes proliferation of monocytic cells. Pulmonary alveolar macrophages (AM) were originally recognized as phagocytosing scavenger cells (Ham & Cormack 1979), but presently they are also known to initiate and regulate inflammatory and immunological processes in several lung diseases (Herscowitz 1985, Unanue & Allen 1987, Sibille & Reynolds 1990). AM are thought to represent more mature cells of the mononuclear phagocyte system, and to be derived from peripheral blood monocytes (PBM) (Van Furth 1982, Ginsel 1993). As AM are continuously lost (mainly through a transport from the peripheral airways, via the trachea to the pharynx), the local AM population must be constantly replenished.(ABSTRACT TRUNCATED AT 400 WORDS)