Structural Analysis of Human β-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.