Immunolocalisation of desmoglein-1 in equine muzzle skin

Desmogleins (Dsgs) are glycoproteins of the cadherin family that allow the formation of desmosomes via a Ca2+-dependent homophilic interaction. Desmosomes are cell-cell adhesion systems that contribute to the mechanical integrity of epidermis by linking to keratin intermediate filaments and, therefore, connecting the cytoskeleton of adjacent keratinocytes (Cozzani et al. 1994). On light microscopy, desmosomes appear as intercellular bridges. On electron microscopy they consist of symmetrical disc-like structures, which link the intermediate filaments system within cells to the plasma membrane and to adjacent cells (North et al. 1999). Four isoforms of Dsgs have been described in human (Whittock 2003), one in bovine (Koch et al. 1990; Puttagunta et al. 1994), 2 in canine (Muller et al. 2000; Aoki et al. 2002), 6 in murine (Whittock 2003) and, recently, one in porcine (Nishifuji et al. 2005) species. The production of autoantibodies against desmoglein-1 (Dsg-1) leads to the loss of epidermal cell-cell adhesion responsible for pustular lesions in the life-threatening skin disease pemphigus foliaceus (PF) (McMillan and Shimizu 2001). The pathogenesis of PF has been intensively investigated in man and the molecular characteristics of human Dsgs analysed (Mahoney et al. 1999). In the canine species Dsg-1 has been characterised and the hypothesis that this glycoprotein is the target antigen in PF is strongly supported (Suter et al. 1993; Iwasaki et al. 1997; Steeves et al. 2002). However, contrasting evidence concerning a minor role of Dsg-1 in the pathogenesis of canine PF has been reported (Olivry et al. 2006). The first case of equine PF was reported by Barnick and Gutzeit (1891) and since 1980 only a few such reports have been documented in this species (Peter et al. 1981; Messer and Knight 1982; Rothwell et al. 1985; Laing et al. 1992; Wohlsein et al. 1994; Stahli et al. 2005). Recently, Vandenabeele et al. (2004) and Zabel et al. (2005) reviewed equine PF. In horses diagnosis is based mainly on clinical and histopathological features, which strictly resemble those described in other species and on the response to immunosuppressive drugs (Vandenabeele et al. 2004; Zabel et al., 2005). Nevertheless, the presence of Dsg-1 in equine epidermis has never been documented and whether this transmembrane protein is targeted by circulating antibodies in horses with PF is still unknown. This study documents the presence of a pericellular antigen in horse muzzle skin by immunohistochemistry using 2 commercially available monoclonal antibodies raised against bovine Dsg-1-2 and human Dsg-1 and the presence of 2 bands by immunoblotting analyses using anti-human-Dsg-1.