Roles of Macrophages in Wound Healing and Scar Formation in a Rabbit Wound Model
|Keywords||wound healing monocyte/macrophages rabbits Cl2MDP-Lip|
Background and ObjectivePathologic scars mainly include hypertrophic scars and keloid which are unique humandermal fibroproliferative disorders and occur spontaneously or after trauma, inflammation, burninjury and surgery. There are many clinical problems for patients with pathologic scars,including: deformation, pruritus, pain, paresthesia, decrease of sleep quality, limitation ofmovement caused by cicatricial contracture of the joint skin and mental disorder, etc. All ofthese lead to the decrease of quality of life ultimately. The basic problem of plastic surgery isabout the prevention and intervention of scar formation. However, the pathogenesis ofpathologic scars is not well understood and there is no effective method to prevent and treatpathologic scars. Thus, an intensive study of the pathogenesis of pathologic scars is of greatsignificance in the prevention and intervention of scar formation.Recently, with the development of immunohistochemistry, cytobiology and molecularbiochemistry, a lot of studies reveal that the amount and constitution changes of cells,extracellular matrix and cytokine in healing wounds are responsible for the formation anddevelopment of pathologic scars. Since a variety of cells and bioactivators participate in thecourse of wound healing and scar formation and interact with each other, forming a complexsystem, the role of a specific cell population and its subpopulation in wound healing and scarformation is not well understood. Macrophages participate in all phases of wound healing andscar formation and the activated macrophages can regulate the proliferation and apoptosis offibroblasts, the synthesis , degradation of extracellular matrix and angiogenesis throughsynthesizing and secreting multiple bioactivators during wound healing and scar formation.Therefore, it is of great significance to study the roles of macrophages in wound healing andscar formation.This study is to investigate the effects of a systemic macrophage-depletion in the earlyphase of wound healing and scar formation in rabbit ears and to explore the roles andmechanism of macrophages in wound healing and scar formation. MethodsCl2MDP-Lip was injected into the helix vein of rabbit to deplete themonocyte-macrophages systematically. The rabbits were divided into two groups:①Experimental group (n=5), Cl2MDP-Lip (2.5ml/kg) was injected into the helix vein of rabbit onthe day before operation and the first day after operation.②Control group (n=5), 0.1M PBS(2.5ml/kg) was injected in the same way. The wound samples were harvested on day 3, 7, 28,56, 84 after operation respectively. The wound samples were divided into two equal parts. Onepart was fixed with 4% paraform and the other was stored with tissue RNA storage reagent(RNAlater) in -80℃refrigerator for further use. The wound healing and scar formation processwere observed and the hypertrophic extent of scars, macrophages infiltration and the PCNAexpression were examined histologically and immunohistologicallyResults1．Hemorrhagic crusts were formed on the first day after operation and there was noevident wound infection. All wounds healed ultimately, however, the wound healing time ofexperimental group was shorter than that of control group (P<0.05).2．The hypertrophic index reached its maximum on day 28 after operation. Thehypertrophic index of experimental group was higher than that of control group on day 28 andday 56 after operation (P<0.05).3．On day 7 after operation, there was massive infiltration of macrophages in the wound.On day 14 after operation, the number of macrophages in the wound decreased andmacrophages were rarely seen on day 28. The number of macrophage in the wound of controlgroup were higher than that of experimental group on day 7 and day 14 after operation(P<0.01).4．The PCNA expression level in the wound was highest on day 7 after operation anddecreased gradually from then on. The PCNA expression level of experimental group washigher than that of control group on day 7 and day 14 after operation (P<0.05). ConclusionA systemic macrophage-depletion during the early phase of wound healing can promotewound healing and enhance scar formation through stimulating cell proliferation in the healingwounds.