RT Journal Article
SR Electronic
T1 Late Breaking Abstract - Recombinant Panton-Valentine leukocidin induced dysregulation of cytokines secretion of human alveolar macrophage is not mediated by necrotic effect
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP PA2367
DO 10.1183/13993003.congress-2021.PA2367
VO 58
IS suppl 65
A1 Xiaohan Shi
A1 Yunfeng Shi
A1 Wenxian Zhang
A1 Jingjing Liang
A1 Benquan Wu
YR 2021
UL http://erj.ersjournals.com/content/58/suppl_65/PA2367.abstract
AB Background: Alveolar macrophages (AMs) are the major immunocytes in lung. Panton-Valentine leukocidin (PVL) causes an inflammatory response in AMs, and Toll-like receptor 2 (TLR2) is the key receptor. However, PVL also causes necrosis of AMs. The mechanism by which PVL exerts its effect on pathogenesis to distinguish between a pro-inflammatory and necrotic effect is not completely understoodMethods: Recombinant PVL (rPVL) were prepared by genetic engineering. Limulus test was applied to exclude an impact of LPS. Human AMs (HAMs) were purified from bronchoalveolar lavage fluid. Groups were set according to rPVL concentration and stimulation time, which are low (10nM) or high (100nM) dose for short (6h) or long (24h) time. Cytokines of TNF-α and IL-10 were measured by ELISA. Morphology by phase contrast microscope (PCM) and transmission electron microscope (TEM) were performed to observed necrosis and apoptosis. Rhodamine 123 staining was used for detection of apoptosis. The expression of TLR2 was investigated by RT-qPCR.Results: rPVL cause dysregulation of pro-inflammatory (TNF-α) and anti-inflammatory (IL-10) cytokine release of Ams. Especially stimulated with high concentration for long time, both TNF-α and IL-10 increased remarkable. Cell lysis was observed both under PCM and TEM. However, increased apoptosis was noted more obviously. And the expression of TLR2 was up-regulated along with the concentration and stimulation time of rPVL.Conclusions: rPVL induced dysregulation of cytokines secretion of HAMs is not be mediated by necrotic effect, which could be one of mechanisms for PVL (+) staphylococcus aureus caused severe pneumonia.FootnotesCite this article as: European Respiratory Journal 2021; 58: Suppl. 65, PA2367.This abstract was presented at the 2021 ERS International Congress, in session “Prediction of exacerbations in patients with COPD”.This is an ERS International Congress 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).