Hemoglobin and its derived peptides may play a role in the antibacterial mechanism of the vagina

Hum Reprod. 2009 Jan;24(1):211-8. doi: 10.1093/humrep/den318. Epub 2008 Sep 10.

Abstract

Background: Hemoglobin is a precursor of antibacterial peptides. Our aim was to identify an antibacterial peptide in human endometrium. We tested the antimicrobial activities of hemoglobin and a derived peptide in vitro and in vivo in rats.

Methods: Samples (n = 3) were scraped from the surface of endometrium. Acid-soluble proteins underwent electrophoresis followed by gel overlay assay and reversed-phase high-performance liquid chromatography. Antibacterial activities were determined by agar radial diffusion assay. Purified peptides were further characterized by electrophoresis, mass spectrometry, N-terminal amino acid (AA) sequencing and protein structure analysis. A rat model was used to test the inhibitory activity of human hemoglobin on vaginal infection with Escherichia coli, using one experimental group (intravaginal hemoglobin, n = 9) and three control groups (n = 14). Vaginal histology was studied.

Results: The purified peptide exhibited potent antibacterial activities against E. coli ML-35P. The N-terminal AA sequence was F L S F P T T K T Y, identical to AA 32-41 of the human hemoglobin alpha chain, and it had the same mass (m/z = 6776.8) as the alpha chain 32-93 AA fragment, with at least three alpha-helices. Histology indicated that the hemoglobin group changed significantly compared with the matrix control group (no treatment after infection): the surface layer of stratified squamous epithelium was smoother, inflammatory cell infiltration was relieved in the lamina propria and congestion pattern was decreased.

Conclusions: These results suggest that erythrocytes from endometrium are another source of the antimicrobial molecules. Hemoglobin and its derived peptides may play a role in the host defense against pathogens in human vagina.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / isolation & purification
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use
  • Chromatography, High Pressure Liquid
  • Endometrium / metabolism
  • Escherichia coli / drug effects
  • Escherichia coli Infections / drug therapy
  • Estrous Cycle
  • Female
  • Hemoglobins / chemistry
  • Hemoglobins / pharmacology*
  • Hemoglobins / therapeutic use
  • Humans
  • Microbial Sensitivity Tests
  • Peptides / chemistry
  • Peptides / isolation & purification
  • Peptides / pharmacology
  • Peptides / therapeutic use
  • Rats
  • Rats, Wistar
  • Uterus / pathology
  • Vagina / metabolism
  • Vagina / microbiology*
  • Vagina / pathology

Substances

  • Anti-Bacterial Agents
  • Hemoglobins
  • Peptides