Human leukocyte elastase induces keratinocyte proliferation in vitro and in vivo
Human leukocyte elastase induces keratinocyte proliferation in vitro and in vivo
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DOI：
10.1046/j.0022-202x.2001.01650.x
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发表时间：
2002-01-01
影响因子：
6.5
通讯作者：
Wiedow, O
中科院分区：
文献类型：
--
作者：
Rogalski, C;Meyer-Hoffert, U;Wiedow, O
神经元浸润和表皮过度增生是银屑病的主要组织病理学改变。中性粒细胞含有人白细胞弹性蛋白酶，认为其在中性粒细胞浸润表皮期间释放。由于活性人白细胞弹性蛋白酶已知存在于银屑病病变中，我们感兴趣的是人白细胞弹性蛋白酶是否在体外和体内诱导角质形成细胞过度增殖。在培养的鼠角质形成细胞系PAM-212中，通过5-溴-2 '-脱氧尿苷掺入测定，1 - 30 nM浓度的人白细胞弹性蛋白酶诱导显著增殖。无毛小鼠每天局部应用0.043-434.8 pmol人白细胞弹性蛋白酶/cm 2皮肤，可诱导浓度依赖性表皮过度增殖，3 d内基底角质形成细胞5-溴-2 '-脱氧尿苷掺入增加5倍。过度增殖导致角质形成细胞层增加高达2倍。组织学分析显示有明显的血管舒张，但无炎性浸润。应用2个猪胰弹性蛋白酶（每厘米（2）皮肤3300 pmol）导致与人白细胞弹性蛋白酶观察到的相似的表皮变化。体外和体内的人白细胞弹性蛋白酶的过度增殖作用被取消的弹性蛋白酶抑制剂，如弹力素，antileukoprotease，和α 1-蛋白酶抑制剂。总之，人白细胞弹性蛋白酶在一定浓度下诱导鼠角质形成细胞增殖，该浓度可在银屑病病变的皮肤表面上发现。这些结果可能为银屑病中观察到的表皮过度增殖提供了解释。
Neutrophil infiltration and epidermal hyperproliferation are major histopathologic changes observed in psoriasis. Neutrophils contain human leukocyte elastase, which is thought to be released during neutrophil infiltration of the epidermis. As active human leukocyte elastase is known to be present in psoriatic lesions we were interested whether human leukocyte elastase induces hyperproliferation in keratinocytes in vitro and in vivo. In the cultured murine keratinocyte cell line PAM-212 concentrations of human leukocyte elastase from 1 to 30 nM induced significant proliferation as determined by 5-bromo-2'-deoxyuridine-incorporation. Daily topical application of 0.043-434.8 pmol human leukocyte elastase per cm 2 skin on hairless mice induced a concentration-dependent epidermal hyperproliferation and an increase in 5-bromo-2'-deoxy-uridine incorporation of up to 5-fold in basal keratinocytes within 3 d. Hyperproliferation resulted in a up to 2-fold increase of keratinocyte layers. Histologic analysis revealed marked vasodilatation but no inflammatory infiltrate. Application of 2 porcine pancreatic elastase (3300 pmol per cm(2) skin) resulted in similar epidermal changes as observed for human leukocyte elastase. Hyperproliferative effects of human leukocyte elastase in vitro and in vivo were abolished by the addition of elastase inhibitors, such as elafin, antileukoprotease, and alpha1-protease inhibitor. In summary, human leukocyte elastase induces proliferation in murine keratinocytes in concentrations, which can be found on the skin surface of psoriatic lesions. These results may provide an explanation for the epidermal hyperproliferation observed in psoriasis.