Structural analysis of human beta-defensin-1 and its significance in urinary tract infection.
Human beta-defensin-1 (hBD-1) is a 36-amino-acid antimicrobial peptide that functions in the host innate defense. We developed a highly sensitive radioimmunoassay for hBD-1 and identified several hBD-1 peptides in human kidney, urine, and plasma by amino acid sequencing and mass spectrometry. Large quantities of hBD-1 peptides are produced in the kidney, are released into the tubular lumen as 47-amino-acid pro-hBD1, and then undergo proteolytic processing and generate multiple truncated forms. The respective urine and plasma concentrations of hBD-1 in patients with pyelonephritis are 48.1 +/- (SEM) 15.7 pmol/mg creatinine and 2.66 +/- 0.41 pmol/ml, 3.1-fold and 1.8-fold those of normal individuals. hBD-1 is thought to contribute to mucosal defense in the urinary tract. Our findings provide a better understanding of the biosynthesis of this peptide and its pathophysiological significance in infectious diseases.
Hiratsuka
T
T
3rd Department of Internal Medicine, Miyazaki Medical College, Miyazaki, Japan.
Nakazato
M
M
Ihi
T
T
Minematsu
T
T
Chino
N
N
Nakanishi
T
T
Shimizu
A
A
Kangawa
K
K
Matsukura
S
S
D000328:Adult; D000595:Amino Acid Sequence; D000915:Antibody Affinity; D023082:Defensins; D006801:Humans; D007668:Kidney / Q000737:chemistry* / Q000378:metabolism / Q000382:microbiology; D008297:Male; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000097:blood / Q000737:chemistry / Q000652:urine; D021382:Protein Sorting Signals / Q000737:chemistry; D011506:Proteins / Q000032:analysis* / Q000276:immunology / Q000378:metabolism*; D011704:Pyelonephritis / Q000378:metabolism*; D011863:Radioimmunoassay; D014552:Urinary Tract Infections / Q000378:metabolism*; D023083:beta-Defensins
C406407:DEFB1 protein, human; D023082:Defensins; D010446:Peptide Fragments; D021382:Protein Sorting Signals; D011506:Proteins; D023083:beta-Defensins