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(Journal of Leukocyte Biology. 2002;72:1003-1010.)
© 2002 by Society for Leukocyte Biology

Inducible expression of an antimicrobial peptide of the innate immunity in polymorphonuclear leukocytes

Linda Tomasinsig^*,, Marco Scocchi, Carla Di Loreto, Daria Artico and Margherita Zanetti^*,

Dipartimento di
^* Scienze e Tecnologie Biomediche and
Ricerche Mediche e Morfologiche, Università di Udine, Italy; and
Laboratorio Nazionale CIB, AREA Science Park, Trieste, Italy

Correspondence: Margherita Zanetti, Dept. Biomedical Sciences and Technology, University of Udine, P.le Kolbe 4, I-33100 Udine, Italy. E-mail: zanetti{at}icgeb.trieste.it

Epithelia- and leukocyte-associated antimicrobial peptides provide immediate protection against microbial infections by rapidly inactivating potential pathogens. Bac5 is a member of the cathelicidin family of antimicrobial peptides and is stored in the cytoplasmic granules of bovine neutrophils. We investigated the expression of this gene in airway and intestine, and although the gene was not found to be locally expressed in these tissues, a strong Bac5 induction signal was detected by in situ hybridization in neutrophils infiltrating infected lung, consistent with expression of this gene in activated neutrophils. The Bac5 gene was also induced in bovine peripheral neutrophils stimulated with Escherichia coli or purified lipopolysaccharide (LPS) but not in other blood cells and in resting neutrophils. The levels of Bac5 mRNA increased at 12–24 h post-stimulation, and a dose-dependent increase in Bac5 expression was determined in the presence of increasing amounts of LPS. A metabolically labeled product with a molecular weight compatible with that of proBac5 was immunoprecipitated from cell-free media of stimulated neutrophils, suggesting that the newly synthesized polypeptide is released extracellularly. Collectively, these results provide the first evidence that fully differentiated neutrophils are capable of de novo synthesis and secretion of a granule-associated antimicrobial peptide.

Key Words: Bac5 • neutrophil • gene expression

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