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人β-防御素2在热损伤中的表达

Expression of human beta defensin 2 in thermal injury.

作者信息

Milner Stephen M, Bhat Satyanarayan, Buja Maximilian, Gulati Salil, Poindexter Brian J, Bick Roger J

机构信息

Division of Plastic Surgery, The Institute for Plastic and Reconstructive Surgery, Southern Illinois University School of Medicine, P.O. Box 19653, 747 N Rutledge Street, Springfield, IL 62794-9653, USA.

出版信息

Burns. 2004 Nov;30(7):649-54. doi: 10.1016/j.burns.2004.06.001.

Abstract

Sepsis is a common and serious complication of major burn injury and accounts for over 54% of deaths in burn patients. Burns are associated with high levels of circulating pro-inflammatory cytokines and immunosuppression, promoting systemic inflammatory response syndrome (SIRS) and sepsis, for which no effective treatment is currently available. Defensins, a family of cationic, naturally occurring, antimicrobial peptides are important components of the innate immune system, playing a major role in the body's defence by inhibiting activities of bacteria, fungi and enveloped viruses. These natural antimicrobials also chemoattract immature dendritic cells, some types of T and B-lymphocytes, neutrophils and macrophages, and act as an adjuvant, enhancing adaptive immunity. Our prior studies suggested a decreased expression of human beta defensin 2 (HBD2) in burn wounds. Here we have identified HBD2 protein in skin samples of partial and full thickness burns and in normal skin using fluorescence deconvolution microscopy. Images showed that in normal skin the majority of HBD2 is located in the Malpighian layer and, in smaller amounts, in the more superficial layers, a pattern that is absent in burned skin in which the epidermis is destroyed or damaged. However, surviving dermal and subcutaneous layers revealed the presence of HBD2 in a number of other cell types and structures, such as hair follicles and sweat gland acini, but not in vascular endothelium and fat cells. The results of these studies further contribute to an understanding of the role of antimicrobial peptides in the pathophysiology of burn injury, associated immunosuppression and sepsis and the possibility of using these other sites of HBD2 deposition for upregulation of antimicrobial synthesis in the treatment of burns.

摘要

脓毒症是严重烧伤常见的并发症,占烧伤患者死亡人数的54%以上。烧伤与循环中促炎细胞因子水平升高及免疫抑制相关,会引发全身炎症反应综合征(SIRS)和脓毒症,目前尚无有效治疗方法。防御素是一类阳离子天然抗菌肽,是固有免疫系统的重要组成部分,通过抑制细菌、真菌和包膜病毒的活性在机体防御中发挥主要作用。这些天然抗菌物质还能趋化未成熟树突状细胞、某些类型的T和B淋巴细胞、中性粒细胞和巨噬细胞,并作为佐剂增强适应性免疫。我们之前的研究表明烧伤创面中人β防御素2(HBD2)表达降低。在此,我们利用荧光反卷积显微镜在部分厚度和全层厚度烧伤的皮肤样本以及正常皮肤中鉴定出了HBD2蛋白。图像显示,在正常皮肤中,大多数HBD2位于马尔皮基层,少量存在于较浅表层,而在表皮被破坏或受损的烧伤皮肤中则不存在这种模式。然而,存活的真皮和皮下层在许多其他细胞类型和结构中发现了HBD2的存在,如毛囊和汗腺腺泡,但在血管内皮细胞和脂肪细胞中未发现。这些研究结果进一步有助于理解抗菌肽在烧伤损伤病理生理学、相关免疫抑制和脓毒症中的作用,以及利用HBD2沉积的其他部位上调抗菌物质合成以治疗烧伤的可能性。

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