Immunolocalisation of desmoglein‐1 in equine muzzle skin

Desmogleins (Dsgs) are glycoproteins of the cadherin family thatallow the formation of desmosomes via a Ca2+-dependenthomophilic interaction. Desmosomes are cell-cell adhesionsystems that contribute to the mechanical integrity of epidermis bylinking to keratin intermediate filaments and, therefore, connectingthe cytoskeleton of adjacent keratinocytes (Cozzani et al. 1994).On light microscopy, desmosomes appear as intercellular bridges.On electron microscopy they consist of symmetrical disc-likestructures, which link the intermediate filaments system withincells 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 inmurine (Whittock 2003) and, recently, one in porcine (Nishifuji etal. 2005) species. The production of autoantibodies againstdesmoglein-1 (Dsg-1) leads to the loss of epidermal cell-celladhesion responsible for pustular lesions in the life-threateningskin disease pemphigus foliaceus (PF) (McMillan and Shimizu2001). The pathogenesis of PF has been intensively investigated inman and the molecular characteristics of human Dsgs analysed(Mahoney et al. 1999). In the canine species Dsg-1 has beencharacterised and the hypothesis that this glycoprotein is the targetantigen in PF is strongly supported (Suter et al. 1993; Iwasaki etal. 1997; Steeves et al. 2002). However, contrasting evidenceconcerning a minor role of Dsg-1 in the pathogenesis of canine PFhas been reported (Olivry et al. 2006).The first case of equine PF was reported by Barnick andGutzeit (1891) and since 1980 only a few such reports have beendocumented in this species (Peter et al. 1981; Messer and Knight1982; Rothwell et al. 1985; Laing et al. 1992; Wohlsein et al.1994; Stahli et al. 2005). Recently, Vandenabeele et al. (2004) andZabel et al. (2005) reviewed equine PF.In horses diagnosis is based mainly on clinical andhistopathological features, which strictly resemble those describedin other species and on the response to immunosuppressive drugs(Vandenabeele et al. 2004; Zabel et al., 2005). Nevertheless, thepresence of Dsg-1 in equine epidermis has never beendocumented and whether this transmembrane protein is targetedby circulating antibodies in horses with PF is still unknown.This study documents the presence of a pericellular antigen inhorse muzzle skin by immunohistochemistry using 2commercially available monoclonal antibodies raised againstbovine Dsg-1-2 and human Dsg-1 and the presence of 2 bands byimmunoblotting analyses using anti-human-Dsg-1