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Abstract

Alveolar macrophages (AM) obtained by bronchoalveolar lavage (BAL) are widely used to study pulmonary macrophage-mediated immune responses. However, questions remain as to whether AM fully represents macrophage function in the lung. This study was performed to determine the contribution of lung tissue interstitial macrophages (IMs) to lung immunity that is absent in BAL sampling. In vivo BrdU injection was performed to assess kinetics and monocyte/tissue-macrophage turnover in Indian rhesus monkeys (Macaca mulatta). Pulmonary macrophage phenotypes and cell turnover were analyzed by flow cytometry and immunohistochemistry. Rhesus monkey lung AM and IM constituted approximately 70% of the immune response cells in the lung. AM represented the majority of macrophages (approximately 75-80%) and showed minimal turnover. Conversely, IMs exhibited a high turnover rate similar to blood monocytes during steady-state homeostasis. IMs also showed strong staining for TdT-mediated dUTP nick end labeling (TUNEL), indicating continued migration of blood monocytes displacing IMs undergoing apoptosis. Although AM appears static at steady-state homeostasis, an increased influx of new AM from monocytes/IMs was observed following the BAL procedure. Furthermore, treatment with ex vivo IFN-γ and LPS increased intracellular expression of TNF-α in IM, but not in AM. These results suggest that long-lived AMs obtained from BAL may not represent the full pulmonary spectrum of macrophage responses, and that short-lived IMs may function as an important subset of pulmonary mucosal macrophages and regulate homeostasis suggest that it may help maintain and protect against continued exposure.