Comparison of Integrins in Human Skin, Pig Skin, and Perfused Skin: An In Vitro Skin Toxicology Model

Integrins α2β1, α3β1, and α6β4 are expressed in the epidermis, and play an important role in wound healing and/or epidermal–dermal interaction. These integrins may provide a new perspective into the understanding of wound healing and vesication. The isolated perfused porcine skin flap (IPPSF) has been shown to be an in vitro model for chemical‐induced vesication. In order to determine whether the IPPSF could be utilized to study skin diseases mediated by integrins, the expression of integrins α2β1, α3β1, and α6β4 was studied in human skin, pig skin, and the IPPSF using immunohistochemical staining. Immunostaining of both α2β1 and α3β1 was primarily located at the periphery of the basal keratinocytes in human skin. Similarly, α2β1 was expressed in the stratum basale layer of the epidermis in both pig skin and the IPPSF after 8 h of perfusion. These antibodies defined the periphery of the pig basal keratinocytes more diffusely than that of human cells. However, the α3 antibody outlined the keratinocytes in all epidermal layers of the IPPSF and in the pig skin. In human skin, pig skin, and the IPPSF, α6β4 stained exclusively at the basal pole of the basal keratinocytes, and showed a continuous linear labeling along the epidermal–dermal junction. The IPPSF showed stronger immunoreactivity with the antibody against β4. Furthermore, the distribution of α6β4 in 5.0 mg/ml of bis‐(2‐chloroethyl) sulfide (sulfur mustard, HD)‐induced blisters was examined in the IPPSF. The α6β4 staining was exclusively located on the epidermal side (roof) of the blister. In addition, α6β4 staining was not linear but disrupted and patchy. These findings suggest that any destruction of α6β4 may weaken the epidermal–dermal junction, thereby leading to HD‐induced vesication. This study demonstrates that the IPPSF expresses similar integrins to those of human skin, and the distribution of α6β4 in the IPPSF blisters caused by HD is comparable to that of some human basement membrane blistering diseases. Therefore, the pig and the IPPSF prove to be ideal models to study the role of integrins in wound healing and blistering diseases occurring at the epidermal–dermal junction. © 1997 John Wiley & Sons, Ltd.