CX3CL1-a macrophage chemoattractant induced by a single bout of exercise in human skeletal muscle
CX3CL1-a macrophage chemoattractant induced by a single bout of exercise in human skeletal muscle
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DOI：
10.1152/ajpregu.00236.2015
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发表时间：
2016-02-01
影响因子：
2.8
通讯作者：
Gustafsson, Thomas
中科院分区：
文献类型：
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作者：
Stromberg, Anna;Olsson, Karl;Gustafsson, Thomas
单核细胞/巨噬细胞（MO/M Phi s）被认为是骨骼肌修复和重塑的关键。这归因于它们的促血管生成潜力、生长因子的分泌和组织碎片的清除。骨骼肌损伤增加了组织中M Phi的数量，并且它们对于肌肉再生的重要性已经得到研究的支持，该研究表明MO/M Phi的耗尽极大地损害了肌肉损伤后的修复。非损伤性运动是否导致诱导表达的MO/M Phi s的化学引诱剂的研究很少。为此，我们分析了一次运动后人骨骼肌中CX（3）CL 1（fractalkine）、CCL 2（MCP-1）和CCL 22（MDC）的表达，所有这些都是由人成肌细胞表达的确定的MO/M Phi趋化因子。在健康个体和年龄匹配的非运动对照组中，在1小时的周期运动后24小时内获得股外侧肌的肌肉活检。一次运动后，人骨骼肌中CX（3）CL 1的mRNA和蛋白水平均增加。不可能区分活检与运动效应之间CCL 2或CCL 22 mRNA水平的变化，并且CCL 22的表达非常低。CX（3）CL 1主要定位于骨骼肌内皮细胞，在运动肌肉组织液刺激的人脐静脉内皮细胞中表达增加。CX（3）CL 1增加THP-1单核细胞（人类急性单核细胞白血病细胞系）以及人类原代成肌细胞和肌管中促炎症因子和促血管生成因子的表达。总而言之，这表明CX（3）CL 1参与了内皮细胞和其他肌肉组织细胞之间的串扰机制，并可能促进微环境向更再生环境的转变。
Monocytes/macrophages (MOs/M Phi s) 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 M Phi s in the tissue, and their importance for muscle regeneration has been supported by studies demonstrating that depletion of MOs/M Phi s greatly impairs repair after muscle injury. Whether noninjurious exercise leads to induced expression of chemoattractants for MOs/M Phi s 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/M Phi 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.