title: Complement deficiency promotes cutaneous wound healing in mice.
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.
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;
authors.forename: Stavros
authors.initials: S
authors.lastname: Rafail
authors.affiliation: 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;
authors.forename: Ioannis
authors.initials: I
authors.lastname: Kourtzelis
authors.affiliation: Second Department of Pathology, School of Medicine, University of Athens, Athens, 124 62 Greece; and.
authors.forename: Periklis G
authors.initials: PG
authors.lastname: Foukas
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;
authors.forename: Maciej M
authors.initials: MM
authors.lastname: Markiewski
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;
authors.forename: Robert A
authors.initials: RA
authors.lastname: DeAngelis
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;
authors.forename: Mara
authors.initials: M
authors.lastname: Guariento
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;
authors.forename: Daniel
authors.initials: D
authors.lastname: Ricklin
authors.affiliation: Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Grice
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104; lambris@upenn.edu.
authors.forename: John D
authors.initials: JD
authors.lastname: Lambris
mesh_terms: D000818:Animals; D003176:Complement C3 / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D015936:Complement C5a / Q000235:genetics / Q000276:immunology; D003165:Complement System Proteins / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018448:Models, Immunological; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000276:immunology; D011951:Receptors, Complement / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000276:immunology* / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D014945:Wound Healing / Q000235:genetics / Q000276:immunology*
chemical_list: D003176:Complement C3; D011951:Receptors, Complement; D015936:Complement C5a; D003165:Complement System Proteins