Abstract
BackgroundThe acute inhalation of endotoxin mimicks several aspects of the inflammation related to chronic obstructive pulmonary disease (COPD). The aim of the current study was to identify and to validate biomarkers of endotoxin-induced airways’ inflammation.MethodsThe cellular count in the induced-sputum, was measured before and after an inhalation of 20 mcg endotoxin, in 8 healthy volunteers. A proteomic analysis was applied to identify the more relevant proteins expression, before measurement by ELISA. The amplitude and the repeatability of the markers were evaluated among another population of 12 healthy subjects.ResultsThere was a significant rise of viable cells (p <0.01), macrophages (p <0.05), and neutrophils (p <0.02) 24 hours after endotoxin inhalation, and of neutrophils (p <0.02) and lymphocytes (p <0.05) at 6 hours. Among the highest amplitude responses, the two dimensional electrophoretic separation shown proteolytic activity and overexpression of protein spots. By MALDI-TOF mass spectrometry, the last were identified as calgranulin A and B. The expression of the bioactive A/B heterodimeric complex was confirmed by ELISA both in the sputum (p <0.01) and at the blood level (p <0.01). The intra-subject repeatability of the sputum calgranulin A/B was highly significant (p <0.0001).ConclusionIn healthy subjects, the inhalation of endotoxin induced expression of sputum calgranulin A/B that could be a biomarker of the endotoxin response/exposure.
Highlights
The acute inhalation of endotoxin mimicks several aspects of the inflammation related to chronic obstructive pulmonary disease (COPD)
The rise of log Polymorphonuclear neutrophils (PMN) was significant 6 and 24 hours after LPS, while the lymphocytes rose at 6 hours and the macrophages at 24 hours (Figure 1)
The present study confirmed that the changes in the cells count and the protein concentration induced by an endotoxin inhalation, is highly variable between subjects [8,9], this individual variability being associated with several gene polymorphisms [19,20]
Summary
The acute inhalation of endotoxin mimicks several aspects of the inflammation related to chronic obstructive pulmonary disease (COPD). The aim of the current study was to identify and to validate biomarkers of endotoxin-induced airways’ inflammation. Endotoxin and its purified derivative lipopolysaccharide (LPS) are pro-inflammatory constituents from Gramnegative bacteria, present in a variety of occupational and home environments [1] and in cigarette smoke [2]. LPS is signalling through the Toll-like receptor-4 (%TLR4), expressed by the stromal cells of the lung [3]. An acute inhalation of LPS produces fever and flu-like symptoms, a rise of sputum polymorphonuclear neutrophils (sPMN) and inflammatory mediators, In the present study, larger responders to LPS inhalation were selected among a group of healthy subjects. Instead of measurement of a number of markers of cells activation, a proteomic analysis was applied to identify possible markers of the lung injury among the selected subjects and to evaluate the saliva contamination. Afterwards, the repeatability of the biomarker was evaluated in both sputum and serum
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