Bronchial Epithelial Cell-derived Cytokines (G-CSF and GM-CSF Promote the Survical of Peripheral Blood Neutrophils In Vitro
- 1 November 1992
- journal article
- Published by American Thoracic Society in American Journal of Respiratory Cell and Molecular Biology
- Vol. 7 (5), 507-514
- https://doi.org/10.1165/ajrcmb/7.5.507
Abstract
Neutrophil accumulation in the respiratory tract occurs in a variety of inflammatory disorders, particularly those associated with cigarette smoking. We examined whether bronchial epithelial cells could contribute to this accumulation through the production of factors that increased the survival of neutrophils. Pure primary cultures of human bronchial epithelial cells (HBEC) were used to generate conditioned medium (CM), and the effect of this CM on the survival of neutrophils in vitro was examined. When neutrophils were cultured in control medium, survival was 8.7 ± 1.7% at 72 h. In contrast, culture of neutrophils in CM resulted in a dose-dependent increase in survival: 22.6 ± 5.5, 43.6 ± 4.2, and 64 ± 3.8% in 1, 10, and 50% CM respectively (mean ± SEM; P < 0.05). As evidenced by the examination of neutrophil DNA, this prolongation of survival was associated with suppression of apoptosis. Cytokines with known actions on neutrophil biology identified in the CM included granulocyte colony-stimulating factor (G-CSF), granulocyte/macrophage colony-stimulating factor (GM-CSF), and interleukin-8. Through the use of specific neutralizing antibodies, G-CSF and GM-CSF were identified as promoting neutrophil survival. Neutrophil survival was prolonged in the presence of either recombinant human (rh) G-CSF or rhGM-CSF alone in a dose-dependent fashion. In contrast to the response of eosinophils to HBEC-CM, steroid treatment did not prevent the increase in neutrophil survival induced by HBEC-CM. In summary, we show that bronchial epithelial cells markedly increase the survival of human neutrophils in vitro via the release of G-CSF and GM-CSF. In this way, HBEC cells might contribute to the accumulation of neutrophils during chronic inflammation in vivo.Keywords
This publication has 37 references indexed in Scilit:
- Human fibroblasts maintain the viability and augment the functional response of human neutrophils in culture.JCI Insight, 1990
- Haemopoietic colony stimulating factors promote cell survival by suppressing apoptosisNature, 1990
- Neutrophil-activating peptide-1/interleukin 8, a novel cytokine that activates neutrophils.JCI Insight, 1989
- Macrophage phagocytosis of aging neutrophils in inflammation. Programmed cell death in the neutrophil leads to its recognition by macrophages.JCI Insight, 1989
- Interleukin 1 stimulates fibroblasts to synthesize granulocyte-macrophage and granulocyte colony-stimulating factors. Mechanism for the hematopoietic response to inflammation.JCI Insight, 1988
- Recombinant human granulocyte-macrophage colony-stimulating factor stimulates in vitro mature human neutrophil and eosinophil function, surface receptor expression, and survival.JCI Insight, 1986
- Recombinant human TNF induces production of granulocyte–monocyte colony-stimulating factorNature, 1986
- Recombinant Human Granulocyte Colony-Stimulating Factor: Effects on Normal and Leukemic Myeloid CellsScience, 1986
- Purified Human Granulocyte-Macrophage Colony-Stimulating Factor: Direct Action on NeutrophilsScience, 1984
- LEUKOKINETIC STUDIES. II. A METHOD FOR LABELING GRANULOCYTES IN VITRO WITH RADIOACTIVE DIISOPROPYLFLUOROPHOSPHATE (DFP32)*JCI Insight, 1960