Page 1037 - Williams Hematology ( PDFDrive )

1012 Part VII: Neutrophils, Eosinophils, Basophils, and Mast Cells Chapter 66: Disorders of Neutrophil Function 1013

TABLE 66–1. Physical-Chemical and Functional Properties of Neutrophil Granules
Granule Protein Localization Physicochemical Properties Function
Myeloperoxidase Azurophil granule Heme protein, 90-kDa proform The MPO–halide–H O system generates
2
2
(AG) with an internal disulphide bond hypochlorous acid (HOCl), other chlorination
between the 57- and the 13.5-kDa products, tyrosine radicals, and reactive nitro-
subunits, generated by proteolytic gen intermediates, each of which can attack
processing that takes place during the surface membrane of microorganisms
routing to granules
Bacterial permeability-increas- AG 55-kDa protein with high homol- BPI is organized into two largely symmetrical
ing (BPI) protein ogy to the LPS-binding protein of subdomains one of which is responsible for
plasma the binding of lipopolysaccharide (LPS) and for
the antimicrobial activity against Gram-nega-
tive microorganisms
Defensins: three α-defensins; AG 7-kDa proforms processed by Defensins are small, amphipathic, pore-form-
human neutrophil peptides proteolytic cleavage to mature ing, antibacterial cationic peptides with a
(HNPs) 1–3 3-kDa defensins that share a char- broad spectrum of antibacterial activity
acteristic three disulfide bond
motif: 1–6, 2–4, 3–5
Serine proteases of azurophil AG 28-kDa proforms, processed Serine proteases, but both elastase and
granules: elastase, cathepsin to active proteases en route to cathepsin G have direct antibacterial activities
G, proteinase 3, and neu- azurophil granules that are not dependent on their enzymatic
trophil serine protease 4 activity; proteinase 3 liberates the antibacterial
(NSP4); azurocidin (CAP37 peptide LL37 from hCAP-18; HBP is chemotac-
or heparin-binding pro- tic for monocytes; HBP may open endothelial
tein [HBP]) is enzymatically cell tight junctions
inactive
Lysozyme AG ~30%; specific Cationic antimicrobial peptide of Lysozyme cleaves peptidoglycan-polymers of
granules (SG) 14 kDa; in contrast to many neu- bacterial cell walls and displays bactericidal
~50%; gelatinase trophil granule proteins, lysozyme activity toward the nonpathogenic Gram-pos-
granules (GG) is inefficiently targeted to granules itive bacteria Bacillus subtilis; a particular high
~20% and circulates free in plasma in a serum level is characteristic for the myelo-
substantial quantity that reflects monocytic leukemias
the normal myelopoietic activity
Lactoferrin SG 78-kDa iron chelator; member of The antibacterial activity of lactoferrin does
the transferrin protein family with not depend exclusively on its ability to
a high affinity for iron and similar sequester iron. Proteolytic fragments, some of
iron-binding characteristics as which are known as lactoferricin, are directly
ferritin bactericidal
Neutrophil gelatinase-asso- SG 25-kDa N-glycosylated member of NGAL is the first known siderophore-binding
ciated lipocalin (NGAL) or the lipocalin protein family eukaryotic protein; NGAL binds enterochelin/
siderochelin enterobactin with high affinity, and blocks
growth of Escherichia coli by sequestering
siderophore–iron complexes
hCAP-18 SG 18 kDa; only human member of the Stored and released intact; binds endotoxin;
cathelicidin protein family C-terminal antibactericidal peptide, LL-37
released by proteinase 3; active mainly against
Gram-positive bacteria, is chemotactic for T
cells, monocytes, and neutrophils, and has
angiogenetic properties
Neutrophil collagenase SG 75-kDa matrix metalloproteinase 8 Active against types I, II, and III collagen
(MMP-8); like other MMPs, MMP-8 is
stored inactive and must be N-ter-
minally trimmed to remove the
inhibitory peptide
Olfactomedin 4 (OLFM4) SG 65-kDa protein that forms multim- Function is unknown, but OLFM4 is present
ers by disulfide bonding only in a subset (25%) of neutrophils
Gelatinase GG 92-kDa MMP-9; stored inactive Active against type IV collagen
Leukolysin, which is dis- SG ~10%; GG Leukolysin is a 56-kDa glycosyl- Active against fibronectin, chondroitin sulfate
tributed among of resting ~40%; secretory phosphatidylinositol (GPI)-an- proteoglycan, dermatan sulfate proteoglycan
neutrophils vesicles (SV) ~30%; chored membrane-bound MMP
plasma mem- (MT6-MMP/MMP-25)
branes (PM) ~20%
(continued )

Kaushansky_chapter 66_p1005-1042.indd 1012 9/21/15 10:48 AM