Localization of annexins in normal and diseased human skin

Annexins (AX) or lipocortins are a family of calcium and phospholipid binding proteins that have been implicated to play a role in the regulation of inflammation and cellular differentiation. To investigate a potential role of AX in skin disorders we studied the distribution of six different AX in normal human skin (NHS) and several inflammatory and hyperproliferative skin diseases. A distinct staining pattern could only be shown for AX-1 and AX-2. In NHS AX-1-antibody (Ab) displayed a very strong reactivity with eccrine sweat ducts. In the diseases investigated we found a highly increased expression of AX-1 in keratinocytes (KCs) in the vicinity of inflammatory processes such as psoriasis. Furthermore, the AX-1 expression was increased in differentiated squamous cell carcinoma (SCC) whereas undifferentiated SCC and basal cell carcinoma were negative. AX-3, -4, -5, and -6 showed no distinctive expression pattern. Our data demonstrate an abnormal distribution of AX-1 in association with proliferating KCs under inflammatory and neoplastic conditions. Its pattern of reactivity shows similarities to the known distribution of the EGF-receptor kinase, which has been demonstrated to phosphorylate AX-1 with high activity in various cellular systems. These results support the concept that the appearance of AX-1 is linked to a certain level of KC differentiation.