Local cyclical compression modulates macrophage function in situ and alleviates immobilization-induced muscle atrophy

Kumiko Saitou, Masakuni Tokunaga, Daisuke Yoshino, Naoyoshi Sakitani, Takahiro Maekawa, Youngjae Ryu, Motoshi Nagao, Hideki Nakamoto, Taku Saito, Noriaki Kawanishi, Katsuhiko Suzuki, Toru Ogata, Michiru Makuuchi, Atsushi Takashima, Keisuke Sawada, Shunsuke Kawamura, Koichi Nakazato, Karina Kouzaki, Ichiro Harada, Yoshinori IchiharaYasuhiro Sawada

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Physical inactivity gives rise to numerous diseases and organismal dysfunctions, particularly those related to aging. Musculoskeletal disorders including muscle atrophy, which can result from a sedentary lifestyle, aggravate locomotive malfunction and evoke a vicious circle leading to severe functional disruptions of vital organs such as the brain and cardiovascular system. Although the significance of physical activity is evident, molecular mechanisms behind its beneficial effects are poorly understood. Here, we show that massage-like mechanical interventions modulate immobilization-induced pro-inflammatory responses of macrophages in situ and alleviate muscle atrophy. Local cyclical compression (LCC) on mouse calves, which generates intramuscular pressure waves with amplitude of 50 mmHg, partially restores the myofiber thickness and contracting forces of calf muscles that are decreased by hindlimb immobilization. LCC tempers the increase in the number of cells expressing pro-inflammatory proteins, tumor necrosis factor-α and monocyte chemoattractant protein-1 (MCP-1), including macrophages in situ. The reversing effect of LCC on immobilization-induced thinning of myofibers is almost completely nullified when macrophages recruited from circulating blood are depleted by administration of clodronate liposomes. Furthermore, application of pulsatile fluid shear stress, but not hydrostatic pressure, reduces the expression of MCP-1 in macrophages in vitro. Together with the LCC-induced movement of intramuscular interstitial fluid detected by μCT analysis, these results suggest that mechanical modulation of macrophage function is involved in physical inactivity-induced muscle atrophy and inflammation. Our findings uncover the implication of mechanosensory function of macrophages in disuse muscle atrophy, thereby opening a new path to develop a novel therapeutic strategy utilizing mechanical interventions.

Original languageEnglish
Pages (from-to)2147-2161
Number of pages15
JournalClinical Science
Volume132
Issue number19
DOIs
Publication statusPublished - 2018 Oct 1

ASJC Scopus subject areas

  • Medicine(all)

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