CX3CL1—a macrophage chemoattractant induced by a single bout of exercise in human skeletal muscle
Abstract
Monocytes/macrophages (MOs/MΦs) are suggested to be crucial for skeletal muscle repair and remodeling. This has been attributed to their proangiogenic potential, secretion of growth factors, and clearance of tissue debris. Skeletal muscle injury increases the number of MΦs in the tissue, and their importance for muscle regeneration has been supported by studies demonstrating that depletion of MOs/MΦs greatly impairs repair after muscle injury. Whether noninjurious exercise leads to induced expression of chemoattractants for MOs/MΦs is poorly investigated. To this end, we analyzed the expression of CX 3 CL1 (fractalkine), CCL2 (MCP-1), and CCL22 (MDC) in human skeletal muscle after a bout of exercise, all of which are established MO/MΦ chemotactic factors that are expressed by human myoblasts. Muscle biopsies from the musculus vastus lateralis were obtained up to 24 h after 1 h of cycle exercise in healthy individuals and in age-matched nonexercised controls. CX 3 CL1 increased at both the mRNA and protein level in human skeletal muscle after one bout of exercise. It was not possible to distinguish changes in CCL2 or CCL22 mRNA levels between biopsy vs. exercise effects, and the expression of CCL22 was very low. CX 3 CL1 mainly localized to the skeletal muscle endothelium, and it increased in human umbilical vein endothelial cells stimulated with tissue fluid from exercised muscle. CX 3 CL1 increased the expression of proinflammatory and proangiogenic factors in THP-1 monocytes (a human acute monocytic leukemia cell line) and in human primary myoblasts and myotubes. Altogether, this suggests that CX 3 CL1 participates in cross-talk mechanisms between endothelium and other muscle tissue cells and may promote a shift in the microenvironment toward a more regenerative milieu.
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During acute exercise, muscle-secreted exerkines such as fractalkine mobilize immune cells to enhance regeneration in humans, and METRNL increases beige adipose tissue thermogenesis in an animal model.
“During acute exercise, immune cells are mobilized by muscle secretion of exerkines such as fractalkine to enhance regeneration (in humans)133 or meteorin-like (METRNL) to increase beige adipose tissue thermogenesis (animal model)134.”
From Exerkines in health, resilience and disease (2022) · cites this paper as [133]
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- Authors
- Strömberg, A., Olsson, K., Dijksterhuis, J. P., Rullman, E., Schulte, G., & Gustafsson, T.
- Affiliations
- Karolinska Institutet (SE)
- Corresponding author
- Strömberg, Anna
- ORCID
- Venue
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Publisher
- American Physiological Society
- Published
- 2016-02-01
- Volume
- 310
- Issue
- 3
- Pages
- R297-R304
- ISSN
- 0363-6119 (ISSN-L)
- 1522-1490
- OpenAlex
- W2257205425
- Cited by
- 67
- References
- 35
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 9 · 2023: 6 · 2022: 7 · 2021: 8 · 2020: 6 · 2019: 6 · 2018: 3 · 2017: 4 · 2016: 4
- FWCI
- 3.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation)
- Karolinska Institutet (KI)
- Vetenskapsrådet (Swedish Research Council)
- Swedish National Centre for Research in Sports
- KI-NIH Joint PhD program
- Svenska Sällskapet för Medicinsk Forskning (Swedish Society for Medical Research)
- Topics
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Keywords
- fractalkine, skeletal muscle, monocytes/macrophages, MCP-1, CCL22, muscle regeneration, endothelium, myoblasts, pro-inflammatory factors, angiogenic factors, vastus lateralis, THP-1 cells, human umbilical vein endothelial cells, muscle microenvironment
- MeSH terms
- Adult, Bicycling, Biopsy, Chemotaxis, Female, Humans, Macrophages, Male, Muscle Contraction, Random Allocation, RNA, Messenger, Time Factors, Exercise, Up-Regulation, Microdialysis, Muscle Fibers, Skeletal, Chemokine CCL2, Myoblasts, Skeletal, Cell Line, Tumor, Quadriceps Muscle, Chemokine CCL22, Chemokine CX3CL1, Young Adult, Cellular Microenvironment, Human Umbilical Vein Endothelial Cells
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