The antiproliferative effect of lectin from the edible mushroom (Agaricus bisporus) on human keratinocytes: preliminary studies on its use in psoriasis

Lectins or agglutinins are proteins with affinity for specific sugar residu es. Peanut agglutinin (PNA) and the lectin from the edible mushroom (Agaric us bisporus, ABL) both bind to the disaccharide galactosyl beta-1,3-N-acety l galactosamine alpha-. This is expressed in keratinocytes as an O-linked c hain on CD44. a polymorphic membrane glycoprotein. Many lectins are mitogen s and PNA is a mitogen for colonic epithelial cells. However, ABL reversibl y inhibits proliferation of colonic cancer eel lines without cytotoxicity a nd thus has therapeutic potential in situations such as psoriasis where pro liferation is increased. We have therefore investigated the effect of ABL o n the growth of normal human cultured keratinocytes and a human papilloma v irus (HPV)-transformed cell line. In a 5-day dose-response study keratinocy te growth was greatly reduced by 1.0 mu g/mL ABL and completely inhibited b y 3.0 mu g/mL ABL (ANOVA, P < 0.0001). Exposure to 1.0 mu g/mL ABL for only 8 h gave the same growth inhibition as did continued exposure for 3 days. No cytotoxic or morphological changes were observed. An HPV-immortalized ce ll line was relatively resistant to ABL: in a 5-day dose-response study, ex posure to 30 mu g/mL was required to inhibit cell growth completely. Topica l application of ABL 0.01% or 0.1% to normal human skin caused no change in skin erythema, blood flow or thickness compared with vehicle or baseline ( n = 6). ABL 0.1% in white soft paraffin was compared with vehicle in 11 pso riatic patients, using comparative contralateral plaques. Twice daily appli cation for 2 weeks showed no significant difference from vehicle-treated si tes, although the skin thickness of plaques fell from 5.3 +/- 0.4 (n = 11, mean +/- SEM) to 4.1 +/- 0.3 mm. in view of the in vitro results further st udies are warranted, particularly if means can be found to improve the epid ermal penetration of the relatively large ABL molecule (60 kDa).