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.
Paulsen
F P
FP
Department of Anatomy, Christian Albrecht University of Kiel, Germany. fpaulsen@anat.uni-kiel.de
Pufe
T
T
Schaudig
U
U
Held-Feindt
J
J
Lehmann
J
J
Schröder
J M
JM
Tillmann
B N
BN
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000890:Anti-Infective Agents / Q000378:metabolism*; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins / Q000096:biosynthesis* / Q000235:genetics; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003607:Dacryocystitis / Q000378:metabolism* / Q000473:pathology; D023082:Defensins / Q000096:biosynthesis* / Q000235:genetics; D015536:Down-Regulation; D004847:Epithelial Cells / Q000378:metabolism; D005136:Eye Proteins / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007767:Lacrimal Duct Obstruction / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009301:Nasolacrimal Duct / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013666:Tears / Q000378:metabolism
C062991:AZU1 protein, human; D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D002352:Carrier Proteins; D023082:Defensins; D005136:Eye Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; C021623:bactericidal permeability increasing protein