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Macrophage Ablation in CD11b‐diphtheria Toxin Receptor (DTR) Transgenic Mice Impairs Skeletal Muscle Regeneration
Author(s) -
Wang Hanzhou,
Porter Laurel,
Sarwar Zaheer U,
Wells Jason T,
McManus Linda M,
Shireman Paula K
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.614.17
Following muscle injury, monocytes/macrophages can increase tissue damage as well as promote tissue repair. DTR mice were used to investigate the role of macrophages in muscle regeneration after cardiotoxin (CTX) injury. To ablate macrophages, diphtheria toxin (DT; 15ng/g body wt; ip) was given to DTR mice at day 1 (early) or day 4 (late) after CTX injury; control mice received mutant diphtheria toxin (DTm). Early DT treatment resulted in selective macrophage ablation in the injured muscle while neutrophils and monocytes remained intact. Residual necrotic myofibers were increased at day 7 after injury in early DT‐treated mice and associated with smaller regenerated myofibers and greater intermuscular adipocyte accumulation at days 7 and 14 after injury. After late macrophage ablation, necrosis and regenerating myofiber size was intermediate compared to early ablation and control mice. Thus, early macrophage‐dependent activities in injured tissue are required for optimal skeletal muscle regeneration. Funding: Veterans Administration and NIH HL074236