Systemic Delivery of Anti-Integrin αL Antibodies Reduces Early Macrophage Recruitment, Inflammation, and Scar Formation in Murine Burn Wounds.
Systemic Delivery of Anti-Integrin αL Antibodies Reduces Early Macrophage Recruitment, Inflammation, and Scar Formation in Murine Burn Wounds.
复制标题
DOI：
10.1089/wound.2019.1035
复制
发表时间：
2020-10
影响因子：
4.9
通讯作者：
X. Strudwick;Damian H. Adams;Natasha T. Pyne;M. Samuel;R. Z. Murray;A. Cowin
中科院分区：
文献类型：
--
作者：
X. Strudwick;Damian H. Adams;Natasha T. Pyne;M. Samuel;R. Z. Murray;A. Cowin
目的：在伤口愈合的早期阶段增加的巨噬细胞募集导致与升高的纤维化和瘢痕形成相关的过度炎症反应。这种募集依赖于单核细胞表面上的整合素，其调节单核细胞从循环到伤口部位的迁移和外渗，在伤口部位，单核细胞分化成巨噬细胞。本研究的目的是确定抑制单核细胞从循环中外渗到烧伤中是否会减少烧伤中的巨噬细胞数量，并导致炎症和瘢痕形成减少。方法：在小鼠上造成烫伤，并在损伤后第1天通过静脉内递送用整合素α L（α L）功能阻断抗体治疗。使用宏观和微观伤口参数以及炎性细胞标志物、细胞因子和胶原沉积的免疫组织化学来评估抑制巨噬细胞募集到烧伤中的效果。结果如下：在用整合素α L抗体处理后第3天，烧伤伤口相关巨噬细胞减少54.7%，到第7天水平恢复正常。巨噬细胞的减少导致炎症介质（包括肿瘤坏死因子α（TNF α）和IL-10）以及前瘢痕形成转化生长因子β 1（TGF β 1）的减少。这种炎症反应的减少也与α平滑肌肌动蛋白（α SMA）表达减少以及瘢痕形成减少的总体趋势和较低的胶原蛋白I/III比值相关。创新：用整合素α L功能阻断抗体治疗烧伤可减少烧伤创面的炎症。结论：这些结果表明，减少巨噬细胞浸润到烧伤创面可能会导致减少早期炎症反应和烧伤后疤痕形成较少。
Objective: Increased macrophage recruitment in the early stages of wound healing leads to an excessive inflammatory response associated with elevated fibrosis and scarring. This recruitment relies upon integrins on the surface of monocytes that regulate their migration and extravasation from the circulation into the wound site, where they differentiate into macrophages. The aim of this study was to determine if inhibiting monocyte extravasation from the circulation into burns would reduce macrophages numbers in burns and lead to reduced inflammation and scar formation. Approach: Scald burns were created on mice and treated with integrin alpha L (αL) function blocking antibody via intravenous delivery day 1 after injury. The effect of inhibiting macrophage recruitment into the burn was assessed using macro- and microscopic wound parameters as well as immunohistochemistry for inflammatory cell markers, cytokines, and collagen deposition. Results: Burn wound-associated macrophages were reduced by 54.7% at day 3 following treatment with integrin αL antibody, with levels returning to normal by day 7. This reduction in macrophages led to a concomitant reduction in inflammatory mediators, including tumor necrosis factor-alpha (TNFα) and Il-10 as well as a reduction in proscarring transforming growth factor beta 1 (TGFβ1). This reduced inflammatory response was also associated with less alpha smooth muscle actin (αSMA) expression and an overall trend toward reduced scar formation with a lower collagen I/III ratio. Innovation: Treatment of burns with integrin αL function blocking antibodies reduces inflammation in burn wounds. Conclusion: These results suggest that reducing macrophage infiltration into burn wounds may lead to a reduced early inflammatory response and less scar formation following burn injury.