RT Journal Article
SR Electronic
T1 Impact of treatments targeting the GM-CSF pathway on the functions of human pulmonary macrophages
JF ERJ Open Research
JO erjor
FD European Respiratory Society
SP 91
DO 10.1183/23120541.LSC-2022.91
VO 8
IS suppl 8
A1 Hélène Salvator
A1 Mathilde Zrounba
A1 Marion Brollo
A1 Stanislas Grassin-Delyle
A1 Quentin Marquant
A1 Emmanuel Naline
A1 Louis-Jean Couderc
A1 Antoine Magnan
A1 Philippe Devillier
YR 2022
UL http://openres.ersjournals.com/content/8/suppl_8/91.abstract
AB Introduction GM-CSF blocking strategies are being developed for the treatment of chronic inflammatory diseases. Their effects on pulmonary macrophages (PM) are still poorly understood. We studied the effects of an anti GM-CSF monoclonal antibody (anti GM-CSF mAb) and ruxolitinib (Ruxo, Janus Kinase 1/2 inhibitor) on the functions of human MPs (cytokine secretion and phagocytosis capacity).Methods The MPs were isolated from lung specimen by adhesion to the culture support. The GM-CSF was assayed by ELISA in the supernatant of the parenchyma explants and MPs, with or without stimulation by LPS. The MPs were treated for 24 hours with ruxo (0.1 to 10 μM) or an anti GM-CSF mAb (0.05 to 1 μg/ml), before adding LPS (10 ng/ml) or POLY (I:C) (10µg/ml). The cytokines were assayed in the supernatant by ELISA. Phagocytosis was assessed by flow cytometry in the presence of labeled E.Coli bioparticles.Results Lung parenchyma and MPs production of GM-CSF was increased in response to LPS. Ruxo and mAbs did not alter the basal cytokine production by MPs but inhibited in a concentration-dependent way the production of TNF-α, IL1β, IL6, IL10, IL23, CCL2 and CXCL10 induced by LPS and POLY (I:C). The mAbs decreased the LPS and POLY (I:C)-induced production of IL6, IL10 and CCL2 only at the highest concentration and did not modify that of TNF-α nor of CXCL10, IL1β, IL23. The phagocytic activity of MPs was not modulated by ruxolitinib or mAbs.Conclusion Ruxo exerts a potent anti-inflammatory action on human PMs without altering their capacity for phagocytosis. This is reproduced only in part by anti GM-CSF antibodies, suggesting the involvement of other regulatory pathways in the effect of ruxo on MPsFootnotesCite this article as ERJ Open Research 2022; 8: Suppl. 8, 91.This article was presented at the 2022 ERS Lung Science Conference, in session “Poster Session 2”.This is an ERS Lung Science Conference abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).