A murine antibacterial ortholog to human bactericidal/permeability-increasing protein (BPI) is expressed in testis,

Andreas Lennartsson1, Katrien Pieters, Karina Vidovic

  • 1Department of Hematology, BMC, C14, S-221 84 Lund, Sweden.

Insights

Murine bactericidal/permeability-increasing protein (BPI) is structurally and functionally conserved with human BPI. Mouse neutrophils store BPI with antibacterial activity, and it is also expressed in the testis and epididymis.

Area of Science:

  • Immunology
  • Genetics
  • Molecular Biology

Background:

  • Bactericidal/permeability-increasing protein (BPI) is crucial for combating Gram-negative bacteria.
  • Human BPI is stored in neutrophil granulocytes, but its mouse ortholog's expression and function remain uncharacterized.
  • Genes for BPI are located on human chromosome 20 and mouse chromosome 2.

Purpose of the Study:

  • To investigate the structural and functional conservation of BPI between humans and mice.
  • To determine if murine BPI is synthesized in neutrophils and other tissues.

Main Methods:

  • Isolation of a murine full-length cDNA encoding BPI.
  • Analysis of gene structure and amino acid identity/similarity to human BPI.
  • Detection of murine BPI mRNA in various tissues and cell lines.
  • Assessment of BPI protein localization in neutrophils.
  • Evaluation of antibacterial activity of murine BPI against Escherichia coli.

Main Results:

  • A murine BPI ortholog was isolated, sharing 53% amino acid identity and 71% similarity with human BPI.
  • Murine BPI mRNA was detected in testis, epididymis, bone marrow, Sertoli, and promyelocytic cell lines.
  • Murine BPI protein exhibited cytoplasmic, granular localization in mature neutrophils.
  • Overexpression of murine BPI conferred antibacterial activity against Escherichia coli, comparable to human BPI.
  • Murine BPI gene expression in Sertoli and promyelocytic cells was upregulated by all-trans retinoic acid.

Conclusions:

  • Mouse neutrophils store BPI with significant antibacterial activity against Gram-negative bacteria.
  • Murine BPI is expressed in neutrophils, testis, and epididymis, indicating conserved and novel roles.
  • The structural and functional conservation suggests potential for similar therapeutic applications in both species.

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