Format

Send to

Choose Destination
Sci Rep. 2019 Sep 10;9(1):12937. doi: 10.1038/s41598-019-49419-z.

G-CSF and GM-CSF Modify Neutrophil Functions at Concentrations found in Cystic Fibrosis.

Author information

1
Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.
2
Department of Biomedical Sciences and Human Oncology, Section of General Pathology, University of Bari, Bari, Italy.
3
Department of Biomedical Sciences and Human Oncology, Section of Medical Genetics, University of Bari, Bari, Italy.
4
Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari, Italy.
5
Cystic Fibrosis Regional Center, Department of Biomedical and Human Oncology, Pediatrics Section, U.O. "B. Trambusti", Policlinico, University of Bari, Bari, Italy.
6
Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.
7
Department of Biomedical Sciences and Human Oncology, Section of General Pathology, University of Bari, Bari, Italy. pasqualina.montemurro@uniba.it.
8
Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy. massimo.conese@unifg.it.

Abstract

The role of colony stimulating factors (CSFs) in cystic fibrosis (CF) circulating neutrophils has not been thoroughly evaluated, considering that the neutrophil burden of lung inflammation in these subjects is very high. The aim of this study was to assess granulocyte-CSF (G-CSF) and granulocyte-macrophage-CSF (GM-CSF) levels in CF patients in various clinical conditions and how these cytokines impact on activation and priming of neutrophils. G-CSF and GM-CSF levels were measured in sputum and serum samples of stable CF patients (n = 21) and in CF patients with acute exacerbation before and after a course of antibiotic therapy (n = 19). CSFs were tested on non CF neutrophils to investigate their effects on reactive oxygen species (ROS) production, degranulation (CD66b, elastase, lactoferrin, MMP-9), and chemotaxis. At very low concentrations found in CF patients (0.005-0.1 ng/ml), both cytokines inhibited ROS production, while higher concentrations (1-5 ng/ml) exerted a stimulatory effect. While either CSF induced elastase and MMP-9 secretion, lactoferrin levels were increased only by G-CSF. Chemotaxis was inhibited by GM-CSF, but was increased by G-CSF. However, when present together at low concentrations, CSFs increased basal and fMLP-stimulated ROS production and chemotaxis. These results suggest the CSF levels that circulating neutrophils face before extravasating into the lungs of CF patients may enhance their function contributing to the airway damage.

PMID:
31506515
DOI:
10.1038/s41598-019-49419-z
Free full text

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center