当前位置： SCI文献检索 > AMERICAN JOURNAL OF HEMATOLOGY期刊下所有文献 > Proteolytic cleavage of granulocyte colony-stimulating factor and its receptor by neutrophil elastase induces growth inhibition and decreased cell surface expression of the granulocyte colony-stimulating factor receptor.

Proteolytic cleavage of granulocyte colony-stimulating factor and its receptor by neutrophil elastase induces growth inhibition and decreased cell surface expression of the granulocyte colony-stimulating factor receptor.

Abstract：

:Neutrophil elastase (NE) is a serine protease stored in the primary granules of neutrophils that proteolytically cleaves multiple cytokines and cell surface proteins on release from activated neutrophils. Recent reports of mutations in the gene encoding this enzyme in some patients with neutropenic syndromes prompted us to investigate whether granulocyte colony-stimulating factor (G-CSF) and its receptor (G-CSFR) are also substrates for NE. To further address this, we examined the effect of NE on G-CSF and the G-CSFR both in solution and on intact cells. Incubation of recombinant G-CSF or a G-CSFR form corresponding to its extracellular domain with purified NE resulted in rapid proteolytic cleavage of both proteins. Addition of NE to tissue culture medium or pretreatment of G-CSF with NE before its addition to media suppressed the growth of G-CSF-responsive cells. NE also cleaved the G-CSFR on the surface of intact cells resulting in a time-dependent reduction in cell surface expression of the G-CSFR. Notably, decreased G-CSFR surface expression resulting from treatment of cells with NE was also associated with a reduction in cell viability and proliferation in response to G-CSF. These results are the first to demonstrate that G-CSF and G-CSFR are proteolytically cleaved by NE and that NE-induced degradation of these proteins correlates with a reduction in the biologic activity of the cytokine and a decrease in the signaling function of the receptor because of decreased G-CSFR surface expression. These findings provide additional insights into mechanisms by which G-CSF/G-CSFR interactions may be modulated.

journal_name

Am J Hematol

journal_title

American journal of hematology

authors

Hunter MG,Druhan LJ,Massullo PR,Avalos BR

doi

10.1002/ajh.10434

keywords:

subject

Has Abstract

pub_date

2003-11-01 00:00:00

pages

149-55

issue

eissn

0361-8609

issn

1096-8652

journal_volume

pub_type

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Proteolytic cleavage of granulocyte colony-stimulating factor and its receptor by neutrophil elastase induces growth inhibition and decreased cell surface expression of the granulocyte colony-stimulating factor receptor.