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Lung Macrophages Serve as Obligatory Intermediate between Blood Monocytes and Alveolar Macrophages¹

Department of Immunology, Weizmann Institute of Science, Rehovot, Israel

Alveolar macrophages are a unique type of mononuclear phagocytes that populate the external surface of the lung cavity. Early studies have suggested that alveolar macrophages originate from tissue-resident, local precursors, whereas others reported their derivation from blood-borne cells. However, the role of circulating monocytes as precursors of alveolar macrophages was never directly tested. In this study, we show through the combined use of conditional cell ablation and adoptive cell transfer that alveolar macrophages originate in vivo from blood monocytes. Interestingly, this process requires an obligate intermediate stage, the differentiation of blood monocytes into parenchymal lung macrophages, which subsequently migrate into the alveolar space. We also provide direct evidence for the ability of both lung and alveolar macrophages to proliferate.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This study was supported by the MINERVA Foundation. S.J. is the incumbent of the Pauline Recanati Career Development Chair and a scholar of the Benoziyo Center for Molecular Medicine.

² Address correspondence and reprint requests to Dr. Steffen Jung, Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel. E-mail address: s.jung{at}weizmann.ac.il

³ Abbreviations used in this paper: DC, dendritic cell; BAL, bronchoalveolar lavage; BM, bone marrow; DTR, diphtheria toxin receptor; DTx, diphtheria toxin; int, intermediate; i.t., intratracheal; M, macrophage; PCNA, proliferating cell nuclear Ag; wt, wild type.

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