Leucine rich α-2 glycoprotein: A novel neutrophil granule protein and modulator of myelopoiesis

Lawrence J. Druhan, Amanda Lance, Shimena Li, Andrea E. Price, Jacob T. Emerson, Sarah A. Baxter, Jonathan M. Gerber, Belinda R. Avalos

Research output: Contribution to journalArticle

Abstract

Leucine-rich α2 glycoprotein (LRG1), a serum protein produced by hepatocytes, has been implicated in angiogenesis and tumor promotion. Our laboratory previously reported the expression of LRG1 in murine myeloid cell lines undergoing neutrophilic granulocyte differentiation. However, the presence of LRG1 in primary human neutrophils and a role for LRG1 in regulation of hematopoiesis have not been previously described. Here we show that LRG1 is packaged into the granule compartment of human neutrophils and secreted upon neutrophil activation to modulate the microenvironment. Using immunofluorescence microscopy and direct biochemical measurements, we demonstrate that LRG1 is present in the peroxidase-negative granules of human neutrophils. Exocytosis assays indicate that LRG1 is differentially glycosylated in neutrophils, and co-released with the secondary granule protein lactoferrin. Like LRG1 purified from human serum, LRG1 secreted from activated neutrophils also binds cytochrome c. We also show that LRG1 antagonizes the inhibitory effects of TGFβ1 on colony growth of human CD34+ cells and myeloid progenitors. Collectively, these data invoke an additional role for neutrophils in innate immunity that has not previously been reported, and suggest a novel mechanism whereby neutrophils may modulate the microenvironment via extracellular release of LRG1.

Original languageEnglish (US)
Article numbere0170261
JournalPLoS One
Volume12
Issue number1
DOIs
StatePublished - Jan 1 2017
Externally publishedYes

Fingerprint

Myelopoiesis
Lactoferrin
Cytochromes c
Leucine
Modulators
Peroxidase
leucine
neutrophils
Blood Proteins
Tumors
glycoproteins
granules
Assays
Glycoproteins
Microscopic examination
Neutrophils
Chemical activation
Cells
Proteins
proteins

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Druhan, L. J., Lance, A., Li, S., Price, A. E., Emerson, J. T., Baxter, S. A., ... Avalos, B. R. (2017). Leucine rich α-2 glycoprotein: A novel neutrophil granule protein and modulator of myelopoiesis. PLoS One, 12(1), [e0170261]. https://doi.org/10.1371/journal.pone.0170261

Leucine rich α-2 glycoprotein : A novel neutrophil granule protein and modulator of myelopoiesis. / Druhan, Lawrence J.; Lance, Amanda; Li, Shimena; Price, Andrea E.; Emerson, Jacob T.; Baxter, Sarah A.; Gerber, Jonathan M.; Avalos, Belinda R.

In: PLoS One, Vol. 12, No. 1, e0170261, 01.01.2017.

Research output: Contribution to journalArticle

Druhan, LJ, Lance, A, Li, S, Price, AE, Emerson, JT, Baxter, SA, Gerber, JM & Avalos, BR 2017, 'Leucine rich α-2 glycoprotein: A novel neutrophil granule protein and modulator of myelopoiesis', PLoS One, vol. 12, no. 1, e0170261. https://doi.org/10.1371/journal.pone.0170261
Druhan, Lawrence J. ; Lance, Amanda ; Li, Shimena ; Price, Andrea E. ; Emerson, Jacob T. ; Baxter, Sarah A. ; Gerber, Jonathan M. ; Avalos, Belinda R. / Leucine rich α-2 glycoprotein : A novel neutrophil granule protein and modulator of myelopoiesis. In: PLoS One. 2017 ; Vol. 12, No. 1.
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