A PHP Error was encountered

Severity: Warning

Message: file_get_contents(https://...@gmail.com&api_key=61f08fa0b96a73de8c900d749fcb997acc09): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests

Filename: helpers/my_audit_helper.php

Line Number: 143

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 143
Function: file_get_contents

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 209
Function: simplexml_load_file_from_url

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 994
Function: getPubMedXML

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3134
Function: GetPubMedArticleOutput_2016

File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global

File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword

File: /var/www/html/index.php
Line: 316
Function: require_once

Neutrophil elastase downmodulates native G-CSFR expression and granulocyte-macrophage colony formation. | LitMetric

AI Article Synopsis

  • - The granulocyte colony-stimulating factor receptor (G-CSFR) is essential for maintaining neutrophil levels, and this study explores how neutrophil elastase (NE) cleaves G-CSFR, leading to reduced expression and granulocyte production.
  • - Human PMNs were treated with NE, showing a decrease in G-CSFR levels over time, which was confirmed by flow cytometry and western blot analysis, revealing degradation and cleavage fragments.
  • - The results suggest that NE plays a role in negatively regulating granulopoiesis, creating a feedback loop that affects G-CSFR expression beyond traditional controls.

Article Abstract

Background: The granulocyte colony-stimulating factor receptor (G-CSFR) plays a critical role in maintaining homeostatic levels of circulating neutrophils (PMN). The mechanisms modulating G-CSFR surface expression to prevent chronic neutrophilia are poorly understood. Here, we report that neutrophil elastase (NE) proteolytically cleaves the G-CSFR on human PMN and blocks G-CSFR-mediated granulopoiesis in vitro.

Methods: Human peripheral blood PMN isolated from healthy donors were incubated with NE. Expression of the G-CSFR was analyzed by flow cytometry and western blot analyses. Detection of G-CSFR cleavage products from the culture supernatants was also performed. Human bone marrow mononuclear cells were also cultured in the presence or absence of NE to determine its effects on the proliferation of granulocyte-macrophage colony forming units (CFU-GM).

Results: Treatment of PMN with NE induced a time-dependent decrease in G-CSFR expression that correlated with its degradation and the appearance of proteolytic cleavage fragments in conditioned media. Immunoblot analysis confirmed the G-CSFR was cleaved at its amino-terminus. Treatment of progenitor cells with NE prior to culture inhibited the growth of granulocyte-macrophage colony forming units.

Conclusions: These findings indicate that in addition to transcriptional controls and ligand-induced internalization, direct proteolytic cleavage of the G-CSFR by NE also downregulates G-CSFR expression and inhibits G-CSFR-mediated granulopoiesis in vitro. Our results suggest that NE negatively regulates granulopoiesis through a novel negative feedback loop.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2824667PMC
http://dx.doi.org/10.1186/1476-9255-7-5DOI Listing

Publication Analysis

Top Keywords

g-csfr expression
12
granulocyte-macrophage colony
12
g-csfr
10
neutrophil elastase
8
g-csfr-mediated granulopoiesis
8
colony forming
8
proteolytic cleavage
8
expression
5
elastase downmodulates
4
downmodulates native
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!