Schremmer-Danninger Elisabeth, Naidoo Strinivasen, Neuhof Christiane, Valeske Klaus, Snyman Celia, Sander Christian, Bhoola Kanti D, Neuhof Heinz
Department of Clinical Chemistry and Clinical Biochemistry, Hospital of Surgery, Ludwig-Maximilians-University Munich, Nussbaumstrasse 20, D-80336 Munich, Germany.
Biol Chem. 2004 Nov;385(11):1069-76. doi: 10.1515/BC.2004.138.
During dermal injury and inflammation the serine proteases kallikreins cleave endogenous, multifunctional substrates (kininogens) to form bradykinin and kallidin. The actions of kinins are mediated by preferential binding to constitutively expressed kinin-B2 receptors or inducible kinin-B1 receptors. A feature of the kinin-B1 receptors is that they show low levels of expression, but are distinctly upregulated following tissue injury and inflammation. Because recent evidence suggested that kinin-B1 receptors may perform a protective role during inflammation, we investigated the specific occurrence of the kallikrein-kinin components in skin biopsies obtained from normal skin, patients undergoing surgery, basalioma, lichenificated atopic eczema, and psoriasis. The tissue was immunolabeled in order to determine the localisation of tissue pro-kallikrein, kallikrein, kininogen and kinin receptors. The kinin components were visualised in normal, diseased and traumatised skin, except that no labelling was observed for kininogen in normal skin. Of the five types of tissue examined, upregulation of kinin-B1 receptors was observed only in skin biopsies obtained following surgery. In essence, the expression of kinin-B1 receptors did not appear to be enhanced in the other biopsies. Within the multiple steps of the inflammatory cascade in wound healing, our results suggest an important regulatory role for kinin-B1 receptors during the first phase of inflammation following injury.
在皮肤损伤和炎症过程中,丝氨酸蛋白酶激肽释放酶可切割内源性多功能底物(激肽原),形成缓激肽和胰激肽。激肽的作用是通过优先结合组成性表达的激肽B2受体或诱导性激肽B1受体来介导的。激肽B1受体的一个特点是它们的表达水平较低,但在组织损伤和炎症后会明显上调。由于最近的证据表明激肽B1受体在炎症过程中可能发挥保护作用,我们研究了从正常皮肤、接受手术的患者、基底细胞癌、苔藓化特应性皮炎和银屑病患者获取的皮肤活检组织中激肽释放酶-激肽成分的具体情况。对组织进行免疫标记,以确定组织激肽释放酶原、激肽释放酶、激肽原和激肽受体的定位情况。在正常、患病和受伤的皮肤中均可看到激肽成分,不过在正常皮肤中未观察到激肽原的标记。在所检查的五种组织类型中,仅在手术后获取的皮肤活检组织中观察到激肽B1受体上调。实际上,在其他活检组织中激肽B1受体的表达似乎并未增强。在伤口愈合炎症级联反应的多个步骤中,我们的结果表明激肽B1受体在损伤后炎症的第一阶段发挥重要的调节作用。