Rijken F, Kiekens R C M, Bruijnzeel P L B
Department of Dermatology, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands.
Br J Dermatol. 2005 Feb;152(2):321-8. doi: 10.1111/j.1365-2133.2004.06335.x.
The pathophysiology of photoageing of the skin has been studied extensively. Matrix metalloproteinases (MMPs) originating from keratinocytes and fibroblasts are thought to play a primary role in this process. Although neutrophils are potent producers of a wide array of proteolytic substances and are present in sunburned skin, their contribution to the pathophysiology of photoageing has been described only in murine studies.
To determine the role of neutrophils in photoageing of human skin.
Healthy white-skinned volunteers were recruited and their sun-protected buttock skin was exposed to solar-simulated radiation (SSR) in dose-response and time-course studies. Punch biopsies were taken and the influx of neutrophils and the expression of neutrophil elastase and MMPs was studied using immunohistochemical techniques and in situ zymography.
Neutrophil elastase and MMPs were detected only in skin irradiated with erythemogenic doses (> or = 1 minimal erythema doses) of SSR. Immunohistochemical double staining demonstrated neutrophils to be the major source of MMP-1, MMP-8 and MMP-9. In situ zymography showed elastase, collagenase and gelatinase enzyme activity in those cells.
Our study suggests that neutrophils participate in the process of photoageing of human skin as they infiltrate the skin and release enzymatically active elastase (neutrophil elastase), collagenase (MMP-1) and gelatinase (MMP-9).
皮肤光老化的病理生理学已得到广泛研究。源自角质形成细胞和成纤维细胞的基质金属蛋白酶（MMPs）被认为在这一过程中起主要作用。尽管中性粒细胞是多种蛋白水解物质的有力产生者，且存在于晒伤皮肤中，但它们对光老化病理生理学的作用仅在小鼠研究中有所描述。
确定中性粒细胞在人类皮肤光老化中的作用。
招募健康的白皮肤志愿者，在剂量反应和时间进程研究中，将他们受防晒保护的臀部皮肤暴露于模拟太阳辐射（SSR）下。进行打孔活检，使用免疫组织化学技术和原位酶谱分析研究中性粒细胞的浸润情况以及中性粒细胞弹性蛋白酶和基质金属蛋白酶的表达。
仅在接受致红斑剂量（≥1个最小红斑剂量）SSR照射的皮肤中检测到中性粒细胞弹性蛋白酶和基质金属蛋白酶。免疫组织化学双重染色显示中性粒细胞是MMP - 1、MMP - 8和MMP - 9的主要来源。原位酶谱分析显示这些细胞中有弹性蛋白酶、胶原酶和明胶酶的活性。
我们的研究表明，中性粒细胞在浸润皮肤并释放具有酶活性的弹性蛋白酶（中性粒细胞弹性蛋白酶）、胶原酶（MMP - 1）和明胶酶（MMP - 9）时，参与了人类皮肤光老化过程。
