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

Abstract

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.

Dynamics of lung macrophage activation in response to helminth infection

“…However, recent evidence indicates that under certain conditions, lung macrophages do have the capability to divide [52], and the expression and cellular data from this study support this idea. Day 2 PI macrophages expressed elevated levels of a number cell cycle-associated genes (Fig.…”

“…However, this capacity to proliferate appears to be short-lived, as the cell cycle genes are no longer elevated by day 8 PI. Lung macrophages are derived from blood monocytes and take on their unique characteristics only after a period of development in the pulmonary environment [52]. Therefore, it is possible that the capacity to proliferate provides an immediate source of differentiated lung macrophages that can play a role in limiting the extent of inflammation and promoting repair of cellular and structural damage.…”

Nontransformed, GM-CSF–dependent macrophage lines are a unique model to study tissue macrophage functions

“…S2D) levels. Notably, the presence of MARCO, Chl3l, CD11c, and the low levels of CD14 observed here for MPI cells is characteristic for lung AMs as well (12)(13)(14). In addition to cells from wild type (WT) mice, we generated MPI cells, also from TLR4-deficient and human TLR4-expressing mice.…”

Probing in vivo dendritic cell functions by conditional cell ablation

“…26,27 An alternative way to circumvent DTxinduced lethality is the development of protocols that aim at local ablation by restricted toxin delivery, as exemplified by the ablation of alveolar macrophages through intratracheal installation of DTx. 18,19 Clearly, the future of the DTR approach in the investigation of in vivo roles of DCs will lie in its application to defined DC subsets. An example for these 'second-generation' DTR mice that target DC subsets are Langerin-DTR mice that were independently generated by two research teams using the Langerin promoter.…”