Alveolar macrophages (AMs) are resident immune cells of the lung that are critical for host defense. AMs are capable of proliferative renewal, yet their numbers are known to decrease with aging and increase with cigarette smoking. The mechanism by which AM proliferation is physiologically restrained, and whether dysregulation of this brake contributes to altered AM numbers in pathologic circumstances, however, remains unknown. Mice of advanced age exhibited diminished basal AM numbers and contained elevated PGE₂ levels in their bronchoalveolar lavage fluid (BALF) as compared with young mice. Exogenous PGE₂ inhibited AM proliferation in an E prostanoid receptor 2 (EP2)-cyclic AMP-dependent manner. Furthermore, EP2 knockout (EP2 KO) mice exhibited elevated basal AM numbers, and their AMs resisted the ability of PGE₂ and aged BALF to inhibit proliferation. In contrast, increased numbers of AMs in mice exposed to cigarette smoking were associated with reduced PGE₂ levels in BALF and were further exaggerated in EP2 KO mice. Collectively, our findings demonstrate that PGE₂ functions as a tunable brake on AM numbers under physiologic and pathophysiological conditions.

中文翻译：

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PGE2解释了肺泡巨噬细胞自我更新与衰老和吸烟之间的双向变化。

肺泡巨噬细胞（AMs）是肺的驻留免疫细胞，对宿主防御至关重要。AMs能够增殖更新，但已知其数量会随着年龄的增长而减少，并随着吸烟的增加而增加。然而，在病理情况下，AM增生在生理上受到抑制的机制以及该制动器的失调是否会导致AM数量的改变尚不清楚。与年幼小鼠相比，高龄小鼠的基础AM数量减少，支气管肺泡灌洗液（BALF）中的PGE ₂水平升高。外源PGE ₂抑制E前列腺素受体2（EP2）-环AMP依赖方式的AM增殖。此外，EP2基因敲除（EP2 KO）小鼠表现出升高的基础AM数量，其AM抵抗PGE ₂和衰老的BALF抑制增殖的能力。相反，暴露于吸烟的小鼠中AM数量增加与BALF中PGE ₂水平降低有关，而在EP2 KO小鼠中进一步夸大。总的来说，我们的发现表明PGE ₂在生理和病理生理条件下可作为AM数的可调制动器。