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Differential response of macrophage subpopulations to soleus muscle reloading after rat hindlimb suspension
Abstract
The hypothesis that distinct populations of macrophages are associated with muscle necrosis and regeneration was examined in Wistar rat soleus muscle after 10 days of hindlimb suspension and 2, 4, and 7 days after the resumption of weight bearing. Necrosis was identified using histological features, such as muscle fiber infiltration, and regeneration was identified using immunohistochemical techniques for developmental myosin heavy chain (dMHC). Light-microscopic observations show that necrotic fibers in 2-day reloaded soleus muscle were invaded by ED1+ and Ia+ macrophages. The number of invaded fibers in muscles reloaded for 2 days increased to 2.8/mm2 compared with 0.2/mm2 in age-matched normal muscle but returned to control values by the 4th day of resumed weight bearing. In the interstitial spaces of 2-day recovery muscle, ED1+ and Ia+ macrophages numbered 369 and 332/mm2, respectively, compared with 12 and 72/mm2, respectively, in control soleus. After 7 days of reloading, the number of ED1+ cells was similar to that of control. Ia+ macrophages decreased to 240/mm2 at 4 days but after 7 days rose above control values to 429/mm2. ED2+ macrophages in 4- and 7-day reloaded soleus increased 70-80% in the interstitial spaces compared with control but were not observed to infiltrate necrotic muscle fibers at any time points. Immunohistochemistry and immunoblots using a monoclonal anti-dMHC antibody demonstrate a greater proportion of myofibers expressing dMHC isoforms after 4…
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“Following the initial pro-inflammatory phase, a switch to an M2 macrophage phenotype and resolution of the inflammatory response has been shown to occur with the initial stages of differentiation of muscle satellite cells into differentiated skeletal muscle cells [123].”
From Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine (2012) · cites this paper as [123]
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“2010), the absence of phagocytic activity (McLennan 1993), and a supportive effect in myogenesis (St Pierre and Tidball 1994).”
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Libera, L., Martin, B., Massimino, M., & Cantini, M. (1997) · doi:10.1016/s0003-2670(97)00261-4 · Cited by 4
Smith, A. H., & Noyes, F. R. (2019) · Springer eBooks · doi:10.1007/978-3-030-22361-8_7 · Cited by 4
Chapter 63 – Immunological Responses to Muscle Injury
Tidball, J., & Rinaldi, C. (2012) · Elsevier eBooks · doi:10.1016/b978-0-12-381510-1.00063-6 · Cited by 4
Self-citationLomiwes, D. D., Barnes, M., Shaw, O. M., Ngametua, N., Sawyer, G. M., Burr, N. S., & Miller, M. R. (2023) · Journal of Science in Sport and Exercise · doi:10.1007/s42978-023-00227-y · Cited by 5
Boulos, A. N., Elagawany, A. M., Awwad, A., Fouad, G., & El-Rahman, A. A. (2020) · The Egyptian Journal of Histology · doi:10.21608/ejh.2020.24878.1257 · Cited by 3
“After the induction of the muscular damage, a lot of active molecules are released inside the tissue and neutrophils start entering the muscles reaching their highest levels at around 1 day post injury[41].”
BackgroundEffects of Walking and Weight-bearing Exercise on Soleus Muscle in Hindlimb-suspended Rat
Miyata, T., Tanaka, S., & Yamazaki, T. (2011) · doi:10.1589/jpts.23.385 · Cited by 3
Hassan, M. (2017) · IOSR Journal of Dental and Medical Sciences · doi:10.9790/0853-1605035466 · Cited by 2
Molecular Biological Changes in Reloaded Skeletal Muscles after Rat Hindlimb Suspension
Tsuji, K., Inaoka, P., Tanaka, S., & Tachino, K. (2009) · Journal of Physical Therapy Science · doi:10.1589/jpts.21.221 · Cited by 2
Adams, A. T., Davis, Z. G., Browder, K. F., Dearth, C. L., & Goldman, S. M. (2025) · Frontiers in Physiology · doi:10.3389/fphys.2025.1555199 · Cited by 1
“ED2 + macrophages are found withintheECMofinjuredmusclesandareresponsibleforcellsignaling and cytokine production to induce muscle repair and regeneration (St Pierre and Tidball, 1985).”
Martin, K. S., Kahrl, A., Ivanov, B., & Johnson, M. A. (2021) · Journal of Zoology · doi:10.1111/jzo.12880 · Cited by 1
“2b, c; St Pierre & Tidball, 1994).”
Recent research developments in regeneration of skeletal muscle
Sakuma, K., & Yamaguchi, A. (2012) · The Journal of Physical Fitness and Sports Medicine · doi:10.7600/jpfsm.1.401 · Cited by 1
Frenette, J. (2000) · Journal of Anatomy · doi:10.1046/j.1469-7580.2000.19620211.x · Cited by 1
Conducting biological research to advance rehabilitation nursing practice.
Schneider, B. S. P., & Flaskerud, J. (1999) · Rehabilitation Nursing · doi:10.1002/j.2048-7940.1999.tb02166.x · Cited by 1
Naimo, M. A. (2019) · The Research Repository @ WVU (West Virginia University) · doi:10.33915/etd.4094
“(100) found similar results in elderly men and women who completed 12 weeks of training, 16 weeks of detraining, and then 8 weeks of retraining; these individuals were able to recover maximum strength gains, rate of torque development, and functional capacity to levels similar to after the initial training period and…”
Injury of the Musculotendinous Junction
Sullivan, J. C., & Best, T. (2005) · Springer eBooks · doi:10.1007/1-84628-050-8_8 · Cited by 1
Metadata
- Authors
- St Pierre, B. A., & Tidball, J. G.
- Affiliations
- School of Nursing, Department of Physiological Science, University of California, Los Angeles 90024–1527.
- University of California, Los Angeles (US)
- ORCID
- Tidball, J. G.
- Venue
- Journal of Applied Physiology
- Publisher
- American Physiological Society
- Published
- 1994-07-01
- Volume
- 77
- Issue
- 1
- Pages
- 290-297
- ISSN
- 0161-7567 (ISSN-L)
- 8750-7587
- 1522-1601
- OpenAlex
- W1806632103
- Cited by
- 251
- References
- 0
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2023: 5 · 2022: 11 · 2021: 10 · 2020: 10 · 2019: 9 · 2018: 12 · 2017: 8 · 2016: 9 · 2015: 8 · 2014: 11 · 2013: 7 · 2012: 13
- FWCI
- 1.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Applied Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ar040343-12, 1f31nr006503-01)
- National Institute of Nursing Research (NR 06503)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR-40343)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology (medical) › Spaceflight effects on biology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Keywords
- macrophage subpopulations, soleus muscle, hindlimb unloading, muscle unloading, muscle reloading, muscle necrosis, muscle regeneration, ED1 macrophages, weight-bearing recovery
- MeSH terms
- Acid Phosphatase, Animals, Animals, Newborn, Body Weight, Female, Hindlimb, Immunohistochemistry, Macrophages, Organ Size, Immunoblotting, Myosin Subfragments, Rats, Wistar, Gravity, Altered, Muscle, Skeletal, Muscle Fibers, Skeletal, Rats
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