Section on Pulmonary, Critical Care, Allergy, and Immunologic Disease, Department of Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Vermont College of Medicine, Burlington, Vermont, USA.
Physiol Rep. 2024 Sep;12(18):e70052. doi: 10.14814/phy2.70052.
Skeletal muscle dysfunction in critical illnesses leaves survivors weak and functionally impaired. Macrophages infiltrate muscles; however, their functional role is unclear. We aim to examine muscle leukocyte composition and the effect of macrophages on muscle mass and function in the murine acute lung injury (ALI)-associated skeletal muscle wasting model. We performed flow cytometry of hindlimb muscle to identify myeloid cells pre-injury and time points up to 29 days after intratracheal lipopolysaccharide ALI. We evaluated muscle force and morphometrics after systemic and intramuscular clodronate-induced macrophage depletions between peak lung injury and recovery (day 5-6) versus vehicle control. Our results show muscle leukocytes changed over ALI course with day 3 neutrophil infiltration (130.5 ± 95.6cells/mg control to 236.3 ± 70.6cells/mg day 3) and increased day 10 monocyte abundance (5.0 ± 3.4%CD45CD11b day 3 to 14.0 ± 2.6%CD45CD11b day 10, p = 0.005). Although macrophage count did not significantly change, pro-inflammatory (27.0 ± 7.2% day 3 to 7.2 ± 3.8% day 10, p = 0.02) and anti-inflammatory (30.5 ± 11.1% day 3 to 52.7 ± 9.7% day 10, p = 0.09) surface marker expression changed over the course of ALI. Macrophage depletion following peak lung injury increased muscle mass and force generation. These data suggest muscle macrophages beyond peak lung injury limit or delay muscle recovery. Targeting macrophages could augment muscle recovery following lung injury.
危重病中的骨骼肌功能障碍使幸存者虚弱且功能受损。巨噬细胞浸润肌肉，但它们的功能作用尚不清楚。我们旨在研究肌肉白细胞组成以及巨噬细胞对急性肺损伤（ALI）相关骨骼肌消耗模型中肌肉质量和功能的影响。我们对损伤前和损伤后 29 天内的后肢肌肉进行流式细胞术，以鉴定髓系细胞。我们在肺损伤高峰和恢复（第 5-6 天）时与载体对照相比，通过系统和肌肉内氯膦酸盐诱导巨噬细胞耗竭来评估肌肉力量和形态计量学。我们的结果表明，肌肉白细胞在 ALI 过程中发生变化，第 3 天中性粒细胞浸润（对照 130.5±95.6 个细胞/mg 至第 3 天 236.3±70.6 个细胞/mg），第 10 天单核细胞增多（CD45CD11b 第 3 天 5.0±3.4%至第 10 天 14.0±2.6%，p=0.005）。尽管巨噬细胞计数没有显著变化，但促炎（第 3 天 27.0±7.2%至第 10 天 7.2±3.8%，p=0.02）和抗炎（第 3 天 30.5±11.1%至第 10 天 52.7±9.7%，p=0.09）表面标志物表达在 ALI 过程中发生变化。在肺损伤高峰后进行巨噬细胞耗竭可增加肌肉质量和力量产生。这些数据表明，肌肉巨噬细胞在肺损伤高峰后限制或延迟肌肉恢复。针对巨噬细胞可能会增强肺损伤后的肌肉恢复。
