| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Surgery, University of Texas Health Science Center, San Antonio, San Antonio, Texas, United States
2 Surgery, University of Texas Health Science Center, San Antonio, San Antonio, Texas, United States; San Antonio, Texas, United States
3 Surgery, University of Texas Health Science Center, San Antonio, Texas, United States
4 Department of Epidemiology and Biostatistics, University of Texas Health Science Center, San Antonio, San Antonio, Texas, United States
5 Protein Design Labs, Fremont, California, United States
6 Department of Pathology, Univ of Texas Health Science Center, San Antonio,, Texas, United States
* To whom correspondence should be addressed. E-mail: shireman{at}uthscsa.edu.
Chemokines recruit inflammatory cells to sites of injury, but the role of the CC chemokine receptor 2 (CCR2) during regenerative processes following ischemia is poorly understood. We studied injury, inflammation, perfusion, capillary formation, monocyte chemotactic protein-1 (MCP-1) levels, muscle regeneration, fat accumulation and transcription factor activation in hind limb muscles of CCR2-/- and wild type (WT) mice following femoral artery excision (FAE). In both groups, muscle injury and restoration of vascular perfusion were similar. Nevertheless, edema and neutrophil accumulation were significantly elevated in CCR2 -/- compared to WT mice at day 1 post-FAE and fewer macrophages were present at day 3. MCP-1 levels in post-ischemic calf muscle of CCR2-/- animals were significantly elevated over baseline through 14 days post-FAE and were higher than WT mice at days 1, 7, and 14. Additionally, CCR2-/- mice exhibited impaired muscle regeneration, decreased muscle fiber size, and increased intermuscular adipocytes with similar capillaries/mm2 post-injury. Finally, the transcription factors, MyoD and signal transducers of and activators of transcription-3 (STAT3), were significantly increased above baseline but did not differ significantly between groups at any time point post-FAE. These findings suggest that increases in MCP-1, and possibly, MyoD and STAT3, may modulate molecular signaling in CCR2-/- mice during inflammatory and regenerative events. Further, alterations in neutrophil and macrophage recruitment in CCR2-/- mice may critically alter the normal progression of downstream regenerative events in injured skeletal muscle, and may direct myogenic precursor cells in the regenerating milieu towards an adipogenic phenotype.
This article has been cited by other articles:
|
|
 |
|
  M. M. Nickerson, J. Song, J. K. Meisner, S. Bajikar, C. W. Burke, C. W. Shuptrine, G. K. Owens, T. C. Skalak, and R. J. Price Bone Marrow-Derived Cell-Specific Chemokine (C-C Motif) Receptor-2 Expression is Required for Arteriolar Remodeling Arterioscler Thromb Vasc Biol, November 1, 2009; 29(11): 1794 - 1801. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Nedachi, H. Hatakeyama, T. Kono, M. Sato, and M. Kanzaki Characterization of contraction-inducible CXC chemokines and their roles in C2C12 myocytes Am J Physiol Endocrinol Metab, October 1, 2009; 297(4): E866 - E878. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-H. Chiu, M. A. Hornsey, L. Klinge, L. H. Jorgensen, S. H. Laval, R. Charlton, R. Barresi, V. Straub, H. Lochmuller, and K. Bushby Attenuated muscle regeneration is a key factor in dysferlin-deficient muscular dystrophy Hum. Mol. Genet., June 1, 2009; 18(11): 1976 - 1989. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Distasi, J. Case, M. A. Ziegler, M. C. Dinauer, M. C. Yoder, L. S. Haneline, M. C. Dalsing, S. J. Miller, C. A. Labarrere, M. P. Murphy, et al. Suppressed hindlimb perfusion in Rac2-/- and Nox2-/- mice does not result from impaired collateral growth Am J Physiol Heart Circ Physiol, March 1, 2009; 296(3): H877 - H886. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Sun, C. O. Martinez, O. Ochoa, L. Ruiz-Willhite, J. R. Bonilla, V. E. Centonze, L. L. Waite, J. E. Michalek, L. M. McManus, and P. K. Shireman Bone marrow-derived cell regulation of skeletal muscle regeneration FASEB J, February 1, 2009; 23(2): 382 - 395. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. J. Capoccia, A. D. Gregory, and D. C. Link Recruitment of the inflammatory subset of monocytes to sites of ischemia induces angiogenesis in a monocyte chemoattractant protein-1-dependent fashion J. Leukoc. Biol., September 1, 2008; 84(3): 760 - 768. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Zhu, B. Han, J. Tong, C. Ma, J. M. Kimzey, K. R. Underwood, Y. Xiao, B. W. Hess, S. P. Ford, P. W. Nathanielsz, et al. AMP-activated protein kinase signalling pathways are down regulated and skeletal muscle development impaired in fetuses of obese, over-nourished sheep J. Physiol., May 15, 2008; 586(10): 2651 - 2664. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-S. Silvestre, Z. Mallat, A. Tedgui, and B. I. Levy Post-ischaemic neovascularization and inflammation Cardiovasc Res, May 1, 2008; 78(2): 242 - 249. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. D Sin and W D. Reid Is inflammation good, bad or irrelevant for skeletal muscles in COPD? Thorax, February 1, 2008; 63(2): 95 - 96. [Full Text] [PDF]
|
|
|
|
 |
|
 O. Ochoa, D. Sun, S. M. Reyes-Reyna, L. L. Waite, J. E. Michalek, L. M. McManus, and P. K. Shireman Delayed angiogenesis and VEGF production in CCR2 / mice during impaired skeletal muscle regeneration Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2007; 293(2): R651 - R661. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Arnold, A. Henry, F. Poron, Y. Baba-Amer, N. van Rooijen, A. Plonquet, R. K. Gherardi, and B. Chazaud Inflammatory monocytes recruited after skeletal muscle injury switch into antiinflammatory macrophages to support myogenesis J. Exp. Med., May 14, 2007; 204(5): 1057 - 1069. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
