Alveolar macrophage replication. One mechanism for the expansion of the mononuclear phagocyte population in the chronically inflamed lung

As bstract. Within any chronically inflamed tis-sue, there is an increased number of macrophages, plu-ripotential phagocytic cells that, while critical to host de-fenses, are also able to profoundly damage parenchymal structure and function. Because of their central role in the inflammatory response, considerable attention has been focused on the mechanisms resulting in an expansion of the macrophage population within an inflamed tissue. Although recruitment of precursor monocytes from the circulation into inflamed tissues clearly plays an important role in macrophage accumulation, it is also possible that replication of tissue macrophages contributes to the ex-pansion of macrophage numbers in inflammation. Be-cause of the accessibility of tissue macrophages with the technique of bronchoalveolar lavage, the lung provides an ideal opportunity to test this hypothesis in humans. To accomplish this, bronchoalveolar lavage was per-formed to obtain alveolar macrophages from normals (n = 5) and individuals with chronic lung inflammation (normal smokers [n = 5], idiopathic pulmonary fibrosis [n = 13], sarcoidosis [n = 18], and other chronic interstitial lung disorders [n = 1 1]). Alveolar macrophage replication was quantified by three independent methods: (a) DNA synthesis, assessed by autoradiographic analysis of macrophages cultured for 16 h in the presence of [3H]thymidine; (b) DNA content, assessed by flow cy-tometric analysis of macrophages fixed immediately after recovery from the lower respiratory tract; and (c) cell division, assessed by cluster formation in semisolid me-dium. While the proportion of replicating macrophage