Candidacidal activity of synthetic peptides based on the antimicrobial domain of the neutrophil-derived protein, CAP37.

The primary bactericidal domain of CAP37, a cationic antimicrobial protein with potent activity against Gram-negative organisms was previously shown to reside between amino acids 20 through 44 (NQGRHFCGGALIHARFVMTAASCFQ) of the native protein. In this study, we explored the efficacy of four synthetic CAP37 peptide analogs, based on this sequence, against various Candida species including fluconazole-sensitive and -resistant isolates of C. albicans. Three of the peptides demonstrated strong antifungal activity for C. albicans, including fluconazole-resistant isolates of C. albicans and were active against C. guilliermondii, C. tropicalis, C. pseudotropicalis, C. parapsilosis, and C. dubliniensis. The peptides were ineffective against C. glabrata, C. krusei, and Saccharomyces cerevisiae. For C. albicans isolates, the peptides had relatively greater activity against blastoconidia than hyphal forms, although strong antifungal activity was observed with pseudohyphal forms of the various Candida species tested. Kinetic studies demonstrated fungicidal rather than fungistatic activity. These findings indicate that synthetic peptides based on the antimicrobial domain of CAP37 also have activity against eukaryotic organisms suggesting a broader range of activity than originally demonstrated and show for the first time their potent fungicidal activity.

Modulation of corneal epithelial cell functions by the neutrophil-derived inflammatory mediator CAP37.

PURPOSE: To investigate the effect of CAP37, an inflammatory mediator in neutrophils, on three important events in corneal wound healing: proliferation, migration, and adhesion. METHODS: Immortalized human corneal epithelial cells (HCEC) were treated with CAP37, and its effects on migration and proliferation were measured using the modified Boyden chemotaxis chamber and the proliferation assays (CyQUANT; Molecular Probes, Eugene, OR), respectively. Effects on adhesion were determined by measuring upregulation of adhesion molecules belonging to the selectin, integrin, and immunoglobulin superfamily using RT-PCR and flow cytometry. RESULTS: CAP37 promoted proliferation of HCEC in a time- and dose-dependent fashion. CAP37 was maximally chemotactic for HCEC over a range of 1.3 x 10(-8) to 5.2 x 10(-8) M. CAP37 upregulated intercellular adhesion molecule (ICAM)-1, platelet endothelial cell adhesion molecule (PECAM)-1, and integrin molecules alpha3 (CD49c) and beta1 (CD29). Data on migration and ICAM-1 and PECAM-1 upregulation were corroborated using primary human corneal epithelial cells. CONCLUSIONS: CAP37 modulated corneal epithelial cell proliferation and migration and upregulated adhesion molecules involved in leukocyte-epithelial and epithelial-extracellular matrix interactions.