A murine antibacterial ortholog to human bactericidal/permeability-increasing protein (BPI) is expressed in testis, epididymis, and bone marrow.
The bactericidal/permeability-increasing protein (BPI), stored in human neutrophil granulocytes, is cytotoxic against Gram-negative bacteria. Several genes related to BPI cluster on human chromosome 20 and on mouse chromosome 2, but expression and characterization of a BPI ortholog in the mouse have not been reported. We asked whether BPI is structurally and functionally conserved between humans and mice and whether murine BPI might be synthesized in neutrophils as well as in other tissues. We report the isolation of a murine full-length cDNA encoding a 54-kDa protein, showing 53% amino acid identity and 71% similarity, to human BPI. The murine BPI and human BPI genes show a similar exon-intron organization. Murine BPI mRNA was detected in testis, epididymis, and bone marrow, as well as in Sertoli and promyelocytic cell lines. Although levels of BPI mRNA in human and murine testis were comparable, expression in murine bone marrow cells was low as compared with that in human bone marrow. BPI protein showed a cytoplasmic, granular localization in mature neutrophils. BPI gene expression in Sertoli and promyelocytic cells was enhanced several-fold by all-trans retinoic acid. Overexpression of murine BPI in human embryonic kidney 293 cells resulted in antibacterial activity against Escherichia coli, comparable with that obtained with human BPI. In conclusion, it was demonstrated that mouse neutrophils store BPI with antibacterial activity and that murine BPI is also expressed in testis and epididymis.
Lennartsson
Andreas
A
Department of Hematology, BMC, C14, S-221 84 Lund, Sweden.
Pieters
Katrien
K
Vidovic
Karina
K
Gullberg
Urban
U
D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000378:metabolism*; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000302:isolation & purification / Q000378:metabolism; D004822:Epididymis / Q000378:metabolism*; D004926:Escherichia coli / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000737:chemistry; D009928:Organ Specificity; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013737:Testis / Q000378:metabolism*
D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D018076:DNA, Complementary; D008565:Membrane Proteins; D011506:Proteins; D012333:RNA, Messenger; C021623:bactericidal permeability increasing protein