ANTIRECEPTOR ANTIBODIES INHIBIT PSEUDOMONAS-AERUGINOSA BINDING TO THECORNEA AND PREVENT CORNEAL PERFORATION

A polyclonal antibody (pAb) against gangliotetraosylceramide (asialo G M(1)), a glycolipid to which bacterial pili and LPS bind, and a mAb ag ainst a 66 kDa pilus-binding protein purified from adult mouse corneal epithelium were used to determine if antibodies against host receptor s for bacterial adhesins could inhibit bacterial binding to wounded co rneal epithelium and protect ocularly challenged mice from corneal per foration when topically applied. Bacteria were mixed with anti-66 kDa mAb, a mixture of anti-asialo GM(1) pAb and anti-66 kDa mAb, an irrele vant control mAb (anti-human histocompatibility Ag HLA-DR5) or PBS pri or to application to scarified corneas in organ culture. The combinati on of the two antibodies or the anti-66 kDa mAb alone was effective in reducing bacterial adherence compared with either PBS or the antibody control. To determine if these antibodies were protective in vivo, co rneas of C57BL/6J mice were scarified and inoculated with Pseudomonas aeruginosa. Eyes were treated topically with anti-asialo GM(1) pAb, an ti-66 kDa mAb, a mixture of the two or control mouse serum. More serum -treated corneas perforated compared to corneas from any other group ( P less than or equal to 0.005) by 30 days postinfection. Treatment wit h a combination of the two antibodies resulted in significantly less c orneal pathology 30 days p.i. when compared to any other treatment (P less than or equal to 0.005). These data provide evidence that antibod ies against host corneal receptors significantly inhibit bacterial bin ding in vitro and when applied topically in vivo, lessen the severity of ocular disease characteristic of P. aeruginosa keratitis.