Content area
Full Text
To the Editor:
Findings in murine models implicate subpopulations of alveolar macrophages in the pathogenesis of lung injury and fibrosis; however, the relevance of these findings for humans with chronic lung disease is unknown in part because of a lack of proper tools to identify macrophage heterogeneity in the human lung. Here we report a flow cytometry protocol that allows unambiguous identification of alveolar macrophages, interstitial macrophages, and monocytes in the human lung and in bronchoalveolar lavage fluid. We validated this panel using normal lung tissue and tissue from patients with chronic obstructive pulmonary disease and lung fibrosis. We found evidence of heterogeneity within human alveolar macrophage populations, which suggest parallels between murine and human macrophage development and differentiation.
Lung macrophages are essential for maintaining homeostasis in the healthy lung and play an important role in pulmonary diseases (I). For decades, alveolar macrophages, which are abundant in the alveolar space of the normal lung, were considered a homogenous population of cells derived from and continuously replenished by circulating monocytes originating from the bone marrow. In careful studies of murine lung development, several groups of investigators have overturned this paradigm. They discovered that alveolar macrophages originate from fetal monocytes, which populate the lungs during the first days of life (2-4). These "tissue-resident" alveolar macrophages are capable of self-renewal, and they or their daughter cells persist in the lung over the lifespan of the host (I, 2). In addition, a healthy mouse lung contains a small fraction of the monocyte-derived interstitial macrophages and extravasated and intravascular monocytes (2, 5, 6). Various insults can induce recruitment of the monocytes into the lung. These monocytes transition through "interstitial macrophages" before differentiating into monocyte-derived alveolar macrophages, which may persist in the lung after injury (7). Previously, we found that although these monocyte-derived alveolar macrophages are phenotypically similar to tissue-resident alveolar macrophages, there were small differences in their surface marker expression after injury, suggesting that subtle changes in surface markers might distinguish monocyte-derived from tissue-resident macrophages (8).
Although human macrophages are less well studied, the murine data predict the presence of at least three distinct populations of monocytes or macrophages in the human lung: alveolar macrophages, interstitial macrophages, and monocytes. Using workflows and protocols we developed in mice, we generated a...