title: 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 CX3CL1 (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. CX3CL1 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. CX3CL1 mainly localized to the skeletal muscle endothelium, and it increased in human umbilical vein endothelial cells stimulated with tissue fluid from exercised muscle. CX3CL1 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 CX3CL1 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.
authors.affiliation: Division of Clinical Physiology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; and anna.stromberg@ki.se.
authors.forename: Anna
authors.initials: A
authors.lastname: Strömberg
authors.affiliation: Division of Clinical Physiology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; and.
authors.forename: Karl
authors.initials: K
authors.lastname: Olsson
authors.affiliation: Section of Receptor Biology and Signaling, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Jacomijn P
authors.initials: JP
authors.lastname: Dijksterhuis
authors.affiliation: Division of Clinical Physiology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; and.
authors.forename: Eric
authors.identifier: http://orcid.org/0000-0003-2854-7262
authors.initials: E
authors.lastname: Rullman
authors.affiliation: Section of Receptor Biology and Signaling, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Schulte
authors.affiliation: Division of Clinical Physiology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; and.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gustafsson
mesh_terms: D000328:Adult; D001642:Bicycling; D001706:Biopsy; D045744:Cell Line, Tumor; D060833:Cellular Microenvironment; D018932:Chemokine CCL2 / Q000378:metabolism; D054422:Chemokine CCL22 / Q000378:metabolism; D054428:Chemokine CX3CL1 / Q000235:genetics / Q000378:metabolism*; D002633:Chemotaxis; D015444:Exercise / Q000502:physiology*; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D009119:Muscle Contraction; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D032448:Myoblasts, Skeletal / Q000378:metabolism; D052097:Quadriceps Muscle / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D013997:Time Factors; D015854:Up-Regulation; D055815:Young Adult
chemical_list: C111835:CCL2 protein, human; C515482:CCL22 protein, human; C515538:CX3CL1 protein, human; D018932:Chemokine CCL2; D054422:Chemokine CCL22; D054428:Chemokine CX3CL1; D012333:RNA, Messenger
keywords: cross-talk; endothelium; exercise; fractalkine; skeletal muscle