Neutrophil granules: heterogeneity of their contents reflects targeting by timing

Nauseef, William M.

doi:10.1002/jlb.66.6.867

Cited by 4 publications

(3 citation statements)

References 21 publications

(15 reference statements)

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“…Expression of FUT9 is limited to a small number of cell types, including granulocytes, neurons, and an unidentified cell type in the kidney (48, 51), indicating that the synthesis of Lewis x may be regulated to enable its use as a specific recognition tag. Because neutrophil secondary granule proteins are all synthesized during the same phase of neutrophil development (52, 53), they are all exposed to the same repertoire of glycosylation enzymes and could be expected to receive similar glycosylation to lactoferrin. The distinct carbohydrate recognition events mediated by the selectins and SRCL are made possible by the different pathways of synthesis of the sialyl-Lewis x and Lewis x epitopes from terminal type II N -acetyllactosamine units as follows: sialyl Lewis x is formed by the sequential actions of sialyltransferase ST3GalIV and fucosyltransferase FUT7 (47), and Lewis x is formed by the action of FUT9 and is far more abundant (42).…”

Section: Discussionmentioning

confidence: 99%

Identification of Neutrophil Granule Glycoproteins as Lewisx-containing Ligands Cleared by the Scavenger Receptor C-type Lectin

Graham

Antonopoulos

Hitchen

et al. 2011

Journal of Biological Chemistry

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The scavenger receptor C-type lectin (SRCL) is a glycan-binding receptor that has the capacity to mediate endocytosis of glycoproteins carrying terminal Lewisx groups (Galβ1–4(Fucα1–3)GlcNAc). A screen for glycoprotein ligands for SRCL using affinity chromatography on immobilized SRCL followed by mass spectrometry-based proteomic analysis revealed that soluble glycoproteins from secondary granules of neutrophils, including lactoferrin and matrix metalloproteinases 8 and 9, are major ligands. Binding competition and surface plasmon resonance analysis showed affinities in the low micromolar range. Comparison of SRCL binding to neutrophil and milk lactoferrin indicates that the binding is dependent on cell-specific glycosylation in the neutrophils, as the milk form of the glycoprotein is a much poorer ligand. Binding to neutrophil glycoproteins is fucose-dependent, and mass spectrometry-based glycomic analysis of neutrophil and milk lactoferrin was used to establish a correlation between high affinity binding to SRCL and the presence of multiple clustered terminal Lewisx groups on a heterogeneous mixture of branched glycans, some with poly N-acetyllactosamine extensions. The ability of SRCL to mediate uptake of neutrophil lactoferrin was confirmed using fibroblasts transfected with SRCL. The common presence of Lewisx groups in granule protein glycans can thus target granule proteins for clearance by SRCL. PCR and immunohistochemical analysis confirm that SRCL is widely expressed on endothelial cells and thus represents a distributed system that could scavenge released neutrophil glycoproteins both locally at sites of inflammation or systemically when they are released in the circulation.

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Section: Discussionmentioning

confidence: 99%

Identification of Neutrophil Granule Glycoproteins as Lewisx-containing Ligands Cleared by the Scavenger Receptor C-type Lectin

Graham

Antonopoulos

Hitchen

et al. 2011

Journal of Biological Chemistry

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“…6). It is known that in granulocyte precursors, the timing of transcription determines in which granules the protein products are stored (25,38). For instance, the serine proteases synthesized by primitive myeloid cells are packaged predominantly in primary azurophil granules, whereas granule proteins synthesized by more mature BM neutrophils are more likely packaged in secondary or tertiary granules (39).…”

Section: Articlementioning

confidence: 99%

Serine protease inhibitors serpina1 and serpina3 are down-regulated in bone marrow during hematopoietic progenitor mobilization

Winkler

Hendy

Coughlin

et al. 2005

The Journal of Experimental Medicine

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Mobilization of hematopoietic progenitor cells into the blood involves a massive release of neutrophil serine proteases in the bone marrow. We hypothesize that the activity of these neutrophil serine proteases is regulated by the expression of naturally occurring inhibitors (serpina1 and serpina3) produced locally within the bone marrow. We found that serpina1 and serpina3 were transcribed in the bone marrow by many different hematopoietic cell populations and that a strong reduction in expression occurred both at the protein and mRNA levels during mobilization induced by granulocyte colony-stimulating factor or chemotherapy. This decreased expression was restricted to the bone marrow as serpina1 expression was maintained in the liver, leading to no change in plasma concentrations during mobilization. The down-regulation of serpina1 and serpina3 during mobilization may contribute to a shift in the balance between serine proteases and their inhibitors, and an accumulation of active neutrophil serine proteases in bone marrow extravascular fluids that cleave and inactivate molecules essential to the retention of hematopoietic progenitor cells within the bone marrow. These data suggest an unexpected role for serpina1 and serpina3 in regulating the bone marrow hematopoietic microenvironment as well as influencing the migratory behavior of hematopoietic precursors.

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“…Classically, neutrophils were divided into peroxidase-positive (azurophil or primary) and peroxidase-negative (specific or secondary) cells [3]. Recent studies, however, have revealed heterogeneity in the granule subsets with respect to their formation, content, and mobilization [4]. Currently, secondary granules are subdivided into specific (secondary) and gelatinase (tertiary) granules based on the relative concentrations of lactoferrin and gelatinase, respectively.…”

Section: Introductionmentioning

confidence: 99%

Neutrophil Degranulation and the Effects of Phosphodiesterase Inhibition

Deree

Lall

Melbostad

et al. 2006

Journal of Surgical Research

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Neutrophil granules: heterogeneity of their contents reflects targeting by timing

Cited by 4 publications

References 21 publications

Identification of Neutrophil Granule Glycoproteins as Lewisx-containing Ligands Cleared by the Scavenger Receptor C-type Lectin

Identification of Neutrophil Granule Glycoproteins as Lewisx-containing Ligands Cleared by the Scavenger Receptor C-type Lectin

Serine protease inhibitors serpina1 and serpina3 are down-regulated in bone marrow during hematopoietic progenitor mobilization

Neutrophil Degranulation and the Effects of Phosphodiesterase Inhibition

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