Inflammation and wound repair

Abstract

Wound repair requires the integration of complex cellular networks to restore tissue homeostasis. Defects in wound repair are associated with human disease including pyoderma gangrenosum, a heterogeneous disorder that is characterized by unhealed wounds and chronic inflammation of unclear etiology. Despite its clinical importance, there remain significant gaps in understanding how different types of cells communicate to integrate inflammation and wound repair. Recent progress in wound and regenerative biology has been gained by studying genetically tractable model organisms, like zebrafish, that retain the ability to regenerate. The optical transparency and ease of genetic manipulation make zebrafish an ideal model system to dissect multi-cellular and tissue level interactions during wound repair. The focus of this review is on recent advances in understanding how inflammation and wound repair are orchestrated and integrated to achieve wound resolution and tissue regeneration using zebrafish.

Keywords: Chronic wounds; Inflammation; Regeneration; Wound repair.

Fig. 1.

Schematic of innate immune inflammation induced by wounding in zebrafish. A) Wounding induces neutrophil recruitment through different cues including a tissue-scale gradient of hydrogen peroxide, cellular swelling-induced production of non-canonical arachadonate metabolites, and IL-8 production. B) Recruitment of macrophages occurs after neutrophils, and the cues are not well defined. After recruitment, neutrophils can reverse migrate from the damaged tissue, the function of which is unknown. C) Resolution is regulated by neutrophil reverse migration, and neutrophil apoptosis accompanied by a resolution of wound signals including hydrogen peroxide. D) Wound debridement by macrophages further contributes to wound resolution and regeneration. Macrophages phagocytose apopotic neutrophils to mediate resolution.