Detection of natural peptide antibiotics in human nasolacrimal ducts.

Objective: To determine the expression and production of antimicrobial peptides by mucosal cells of the lacrimal passage in healthy and pathologic states.

Methods: Detection of bactericidal-permeability-increasing protein (BPI), heparin-binding protein (CAP37), human cationic antimicrobial protein (LL-37), human alpha-defensin 5 (HD5), human alpha-defensin 6 (HD6), human beta-defensin 1 (HBD-1), and human beta-defensin 2 (HBD-2) was performed by reverse transcription-polymerase chain reaction (RT-PCR). Intracellular deposition of lysozyme, lactoferrin, secretory phospholipase A(2), human neutrophil defensins (HNP-1, -2, and -3), human beta-defensin 1 (HBD-1), and human beta-defensin 2 (HBD-2) was analyzed immunohistochemically. Samples were obtained from 15 patients by surgery and from 10 cadavers.

Results: RT-PCR revealed BPI, CAP37, and HBD-1 mRNA in samples of healthy nasolacrimal duct epithelium. Additionally, HBD-2 mRNA was detected in epithelial samples from patients with dacryocystitis. Messenger RNAs for LL-37 and alpha-defensin 5 and 6 were absent in all samples investigated. Immunohistochemistry revealed lysozyme, lactoferrin, secretory phospholipase A(2), and HNP-1, -2, and -3 to be present in all samples, whereas HBD-1 was present only in some of the healthy and inflamed samples. Immunoreactive HBD-2 peptide was visible only in some of the inflamed samples.

Conclusions: The data suggest that the human efferent tear ducts produce a broad spectrum of antimicrobial peptides. Under inflammatory conditions, changes in the expression pattern occurred, revealing induction of the human inducible defensin HBD-2 and in some cases downregulation of HBD-1 and CAP37. Antimicrobial peptides have a therapeutic potential in dacryocystitis, in that they have a broad spectrum of antimicrobial activity and accelerate epithelial healing. However, caution is appropriate, because defensins also promote fibrin formation and cell proliferation, which are key elements in scarring processes, such as dacryostenosis.