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p15s (15-kD antimicrobial proteins) are stored in the secondary granules of
Rabbit granulocytes: implications for antibacterial synergy with the
bactericidal/permeability-increasing protein in inflammatory fluids
K Zarember, P Elsbach, K Shin-Kim and J Weiss
Department of Microbiology, School of Medicine, New York University, NY,
USA.
The bactericidal potency toward complement-resistant Escherichia coli of
bactericidal/permeability-increasing protein (BPI) released from
polymorphonuclear leukocytes (PMNs) in glycogen-induced inflammatory
peritoneal exudates of rabbits is dependent on synergy with extracellular
p15s. This synergy depends on the high molar ratio of p15s to BPI in the
extracellular fluid (approximately 50:1), which greatly exceeds the
intracellular ratio (approximately 5:1). To explore the possible basis of
the greater accumulation of p15s in inflammatory fluid, we examined the
subcellular localization of BPI and p15 in PMNs. Immunogold electron
microscopy confirmed the storage of BPI in primary granules and showed that
p15s are stored in secondary granules. Reverse- transcription polymerase
chain reaction of density-fractionated rabbit bone marrow cells verified
that p15s are expressed later than BPI during myeloid differentiation. As
the inflammatory response evolves, p15 mRNA appears earlier in blood and
exudate cells than mRNA for BPI, consistent with release of progressively
less mature precursors from bone marrow. Finally, Ca(2+)-ionophore-mediated
exocytosis of p15s occurs more readily than release of BPI. We therefore
propose that localization of a synergistic partner of BPI (p15s) in more
readily released secondary granules allows the neutrophil to mobilize
potent BPI-dependent antibacterial activity extracellularly without
significant depletion of intracellular BPI stores.
Volume 89,
Issue 2,
pp. 672-679,
01/15/1997
Copyright © 1997 by The American Society of Hematology

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