Processing of seminal plasma hCAP-18 to ALL-38 by gastricsin: a novel mechanism of generating antimicrobial peptides in vagina.
The human cathelicidin, hCAP-18, is expressed both in neutrophils and in epithelial cells. hCAP-18 is processed to the antimicrobial peptide LL-37 by proteinase 3 in neutrophils. hCAP-18 is highly expressed in the epididymis with a subsequent high concentration in seminal plasma where the protein is present in its unprocessed and antimicrobially inactive form. We report here that hCAP-18 in seminal plasma is processed to generate a 38-amino acid antimicrobial peptide ALL-38 by the prostate-derived protease gastricsin when incubated at a pH corresponding to the vaginal pH. In accordance with this, seminal plasma derived hCAP-18 was found in its processed form in the vagina following sexual intercourse. The antimicrobial activity of ALL-38 against a variety of microorganisms tested is equal to that of LL-37. This enzymatic activation of a proantimicrobial substance in seminal plasma following exposure to the vaginal milieu represents a novel mechanism to prevent infection following sexual intercourse.
Sørensen
Ole E
OE
Granulocyte Research Laboratory, the Department of Hematology, Copenhagen University Hospital, Rigshospitalet, DK-2100 Copenhagen, Denmark. sorensen@ucla.edu
Gram
Lone
L
Johnsen
Anders H
AH
Andersson
Emma
E
Bangsbøll
Susanne
S
Tjabringa
G Sandra
GS
Hiemstra
Pieter S
PS
Malm
Johan
J
Egesten
Arne
A
Borregaard
Niels
N
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D001410:Bacillus megaterium / Q000187:drug effects; D001826:Body Fluids / Q000737:chemistry; D054804:Cathelicidins; D011232:Chemical Precipitation; D003075:Coitus; D004591:Electrophoresis, Polyacrylamide Gel; D004926:Escherichia coli / Q000187:drug effects; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008969:Molecular Sequence Data; D010434:Pepsin A / Q000378:metabolism*; D010436:Pepstatins / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology; D012661:Semen / Q000737:chemistry / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000187:drug effects; D014621:Vagina / Q000737:chemistry / Q000378:metabolism
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D010436:Pepstatins; D010446:Peptide Fragments; D011480:Protease Inhibitors; C035121:pepsinostreptin; D010434:Pepsin A; C020557:gastricsin; C031375:pepstatin