Granulocyte macrophage colony-stimulating factor is the main cytokine enhancing survival of eosinophils in asthmatic airways

Abstract

Interleukin (IL)-3, IL-5 and granulocyte macrophage colony-stimulating factor (GM-CSF) prolong the survival of eosinophils, which are conspicuous in asthmatic airways, but it is still controversial which one plays a major role in enhancing the survival of eosinophils in asthmatic airways. The role of these cytokines in airway eosinophilia was investigated using bronchoalveolar lavage (BAL) fluids from 11 symptomatic and nine asymptomatic patients with asthma and eight normal subjects. Eosinophil survival-enhancing activity (ESEA) was measured by a numerical change in viable eosinophils isolated from the peripheral blood of atopic patients and cultured with BAL fluids. ESEA was characterized by neutralization with antibodies to IL-3, IL-5 and/or GM-CSF. The differential count of BAL cells was achieved using Diff-Quik stain. T-cell subsets and activated T-cells were analysed by flow cytometry with dual stain using monoclonal antibodies to CD3, CD4, CD8 and CD25. ESEA was detected in eight of 11 BAL fluids of symptomatic asthma, but not in those of normal controls or asymptomatic asthmatics. In six symptomatic asthmatics, the mean percentage of inhibition in ESEA by anti-GM-CSF was higher than that of anti-IL-5 as well as anti-IL-3 (p<0.05). A mixture of antibodies to IL-3, IL-5 and GM-CSF totally inhibited the ESEA in four cases. The ESEA correlated with the percentage of eosinophils (p<0.05) and that of CD25(+)CD4 lymphocytes (p<0.05) of BAL cells. In conclusion, granulocyte macrophage colony-stimulating factor, rather than interleukin-3 or -5, is associated with eosinophil survival-enhancing activity inside the airways of symptomatic asthmatics. The activation of CD4 lymphocytes is related to the elevation of such activity.

Anti-inflammatory activity of β2-agonists in primary lung epithelial cells is independent of glucocorticoid receptor

“…GM-CSF is able to promote the differentiation, activation and survival of eosinophils and other inflammatory cells, a process triggered by various stimuli, including TNF-a, environmental particles, oxidants etc., that result in the activation of pro-inflammatory transcription factors, such as NF-kB and AP-1, and subsequent transcription of GM-CSF by the airway epithelium [18,27,28]. In the present paper, BUD, FORM and SALM concentrationdependently decreased GM-CSF levels by ,50%.…”

House Dust Mite Allergens and the Induction of Monocyte Interleukin 1β Production That Triggers an IκBζ-Dependent Granulocyte Macrophage Colony-Stimulating Factor Release from Human Lung Epithelial Cells

“…The immunoblots represent three independent experiments, and the error bars represent the mean 6 SEM of six or seven experiments for Mo and three or four experiments for DC and Mf (A) and three experiments (D). *P , 0.05. and eosinophils in the lungs (36), whereas IL-6 induces proliferation and activation of T cells (37). Thus, these cytokines are essential for linking the early innate immune response to the late adaptive immune response of asthma.…”

(R)-Albuterol Elicits Antiinflammatory Effects in Human Airway Epithelial Cells via iNOS

“…For example, ␤ 2 -adrenergic agonists suppress GM-CSF production in macrophages, smooth muscle cells, and epithelial cell lines (7,9,(28)(29)(30). Modulation of GM-CSF is particularly interesting because the epithelium has been suggested as a major source of GM-CSF production, especially in asthmatic airways (31), and GM-CSF levels in bronchoalveolar lavage fluid of individuals with asthma correlate with eosinophilic infiltration and disease severity (32). Mechanisms whereby GM-CSF production is regulated in airway epithelial cells have not been elucidated.…”