Mitogenic lectins from Cephalosporium curvulum (CSL) and Aspergillus oryzae (AOL) mediate host-pathogen interactions leading to mycotic keratitis.

A core-fucose-specific lectin, CSL from Cephalosporium curvulum, has been reported earlier. Here we assign the role for CSL and another lectin AOL, from pathogenic fungus Aspergillus oryzae, in causing mycotic keratitis. CSL and AOL show strong binding to immortalized and primary human corneal epithelial cells (HCECs) which are inhibited by asialofetuin, confirming their glycan-mediated binding. CSL and AOL showed increase in viability at lower concentrations (0.07 µg/ml) whereas at higher concentrations (0.15 µg/ml and 0.30 µg/ml), have inhibitory effect on immortalized HCECs. Lectin-mediated effect was comparable with the effect induced by the Colony Forming Units (CFUs) of C. curvulum and A. oryzae. CFUs induced more than 1.5-fold increase in HCECs proliferation. Both lectins and fungal CFUs induce secretion of proinflammatory cytokines IL6 and IL8 implicated in ocular diseases. This was supported by upregulation of TLR2 and 4 by lectins as revealed by flow cytometry and RT-PCR. CSL and AOL mediate host-pathogen interactions leading to mycotic keratitis. The mechanism of pathogenesis is possibly initiated through surface binding of mycelia through the lectins to TLR2/4 followed by upregulation of proinflammatory cytokines IL6, IL8 and TLR2 and 4. Understanding the mechanism of pathogenesis is of clinical significance in designing and developing therapeutic strategy to control the infection.

Pharmacokinetics, biodistribution and antitumour effects of Sclerotium rolfsii lectin in mice.

Sclerotium rolfsii lectin (SRL) is a lectin isolated from the fungus Sclerotium rolfsii and has exquisite binding specificity towards the oncofetal Thomsen-Friedenreich antigen (TF-Ag; Galß1-3GalNAcα-O-Ser/Thr) and its derivatives. Previous studies have shown that SRL inhibits the proliferation of human colon, breast and ovarian cancer cells in vitro and suppresses tumour growth in mice when introduced intratumourally. The present study assessed the effect of SRL on tumour growth when introduced intraperitoneally in BALB/c nude mice and investigated the pharmacokinetics and biodistribution of SRL in Swiss albino mice. When 9 doses of SRL (30 mg/kg body weight/mice) was administered to BALB/c nude mice bearing human colon cancer HT-29 xenografts, a substantial reduction in tumour size was observed. A 35.8% reduction in tumour size was noted in the treated animals after 17 days. SRL treatment also inhibited angiogenesis, and the tumours from the treated animals were observed to carry fewer blood vessels and express less angiogenesis marker protein CD31, than that from the control animals. Pharmacokinetics and biodistribution analysis revealed that SRL was detected in the serum after 1 h and its level peaked after 24 h. SRL was not detected in any of the organs apart from the kidney where a trace amount was detected after 24 h of SRL injection. No significant changes were observed in any of the biochemical parameters tested including SGOT, SGPT, LDH, CREAT and BUN in the SRL-treated mice compared to these levels in the controls. This suggests that SRL has good potential to be developed as a therapeutic agent for cancer treatment and warrant further investigations in vivo and subsequent clinical trials.