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J Immunol. 2015 Feb 1;194(3):1285-91. doi: 10.4049/jimmunol.1402354. Epub 2014 Dec 29.

Complement deficiency promotes cutaneous wound healing in mice.

Author information

1
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;
2
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104; Abteilung für Klinische Pathobiochemie, Medizinische Fakultät, Technische Universität Dresden, 01307 Dresden, Germany;
3
Second Department of Pathology, School of Medicine, University of Athens, Athens, 124 62 Greece; and.
4
Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
5
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104; lambris@upenn.edu.

Abstract

Wound healing is a complex homeostatic response to injury that engages numerous cellular activities, processes, and cell-to-cell interactions. The complement system, an intricate network of proteins with important roles in immune surveillance and homeostasis, has been implicated in many physiological processes; however, its role in wound healing remains largely unexplored. In this study, we employ a murine model of excisional cutaneous wound healing and show that C3(-/-) mice exhibit accelerated early stages of wound healing. Reconstitution of C3(-/-) mice with serum from C3(+/+) mice or purified human C3 abrogated the accelerated wound-healing phenotype. Wound histology of C3(-/-) mice revealed a reduction in inflammatory infiltrate compared with C3(+/+) mice. C3 deficiency also resulted in increased accumulation of mast cells and advanced angiogenesis. We further show that mice deficient in the downstream complement effector C5 exhibit a similar wound-healing phenotype, which is recapitulated in C5aR1(-/-) mice, but not C3aR(-/-) or C5aR2(-/-) mice. Taken together, these data suggest that C5a signaling through C5aR may in part play a pivotal role in recruitment and activation of inflammatory cells to the wound environment, which in turn could delay the early stages of cutaneous wound healing. These findings also suggest a previously underappreciated role for complement in wound healing, and may have therapeutic implications for conditions of delayed wound healing.

PMID:
25548229
PMCID:
PMC4297721
DOI:
10.4049/jimmunol.1402354
[Indexed for MEDLINE]
Free PMC Article

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