Mechanisms of asthma and allergic inflammationInhaled LPS induces blood release of Clara cell specific protein (CC16) in human beings
Section snippets
Populations
In a group of 15 healthy nonsmoking subjects, plasma samples were obtained before, 6 hours after, and 24 hours after exposure to LPS by inhalation. At 1-week intervals, the population was exposed to saline, 0.5, 5, and 50 μg LPS, in random order. The mean age was 31.1 (±3.0) years; there were 8 female and 7 male subjects.
Another group of 15 healthy nonsmoking subjects (different from the first group) was exposed to 50 μg LPS after a 6-day pretreatment with placebo and methylprednisolone (20
Results
The exposure was well tolerated, and no serious adverse reaction was observed. There was no significant change in temperature and/or spirometry. Four subjects developed slight flulike symptoms.
In the basal state, the mean concentration of plasma CC16 for the 30 subjects from the 2 populations was 7.9 (±0.5) ng/mL, ranging from 2.8 ng/mL to 13.1 ng/mL.
An inhalation of 50 μg LPS induced a significant rise in CC16 plasma concentration. The kinetics of the response, reported in Fig 1, showed no
Discussion
The current study shows that in healthy subjects, an inhalation of LPS results in a dose-related increase in blood CC16 that peaks at 6 hours and normalizes at 24 hours, and that this response is blocked by a pretreatment with oral methylprednisolone.
Acute lung injury by smoke, ozone, and, recently, nitrogen trichloride (NCl3) exposure has also been associated with expression of CC16 at the blood level in human beings21, 22, 23 only a few hours after exposure. Using higher doses of LPS (100
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Urinary CC16, a potential indicator of lung integrity and inflammation, increases in children after short-term exposure to PM<inf>2.5</inf>/PM<inf>10</inf> and is driven by the CC16 38GG genotype
2022, Environmental ResearchCitation Excerpt :The time needed for this increase to occur and to be observed, can vary depending on the source and the levels of the toxicant causing the inflammation. Irritants such as ozone (Alexis et al., 2008; Arsalane et al., 1999; Blomberg et al., 2003; Broeckaert et al., 2000), smoke (Rosenberg and Kalhan, 2012; Stockfelt et al., 2012) and lipopolysaccharides (Doyen et al., 2016; Michel et al., 2005) lead to serum CC16 levels rapidly increasing within a few hours after exposure. Similarly, serum CC16 increased in the first 2 h and lasted up to 24 h after PM2.5 exposure (Wang et al., 2017a).
Nasal epithelium injury by chlorination products and other stressors predicts persistent sensitization to aeroallergens in young schoolchildren
2017, Environmental ResearchCitation Excerpt :When for ethical reasons it is not possible to collect blood (e.g. in schoolchildren), an alternative approach is to use epithelial biomarkers measurable in nasal lavage fluid (NALF) (Sardella et al., 2012, 2013). Studies using these peripheral airway biomarkers have shown that various stressors including air pollutants, strenuous exercise or endotoxin can cause acute or chronic damage to the airway epithelial barriers (Broeckaert and Bernard, 2000; Lagerkvist et al., 2004, Nanson et al., 2001; Michel et al., 2005). Among these stressors, chlorination products (CPs) are of particular interest because these strong oxidants linked to the hygiene of the developed world are well-known for their capacity to breach tight junctions (Bernard, 2007).
Inflammatory response to acute hypoxia in humans
2014, Pulmonary Pharmacology and TherapeuticsCitation Excerpt :This implies hyperpermeability of the alveolocapillary membrane, suggesting that hypoxic exposure alters the function and integrity of the alveolocapillary membrane. CC16 is expressed in pulmonary Clara cells and has been shown in animal [16] and human studies [17] to be a sensitive biomarker of pulmonary epithelial function [18]. In the present study, as shown previously [18], there was a significant decline in CC16 under normoxic conditions during the day, however there was no significant effect of acute hypoxia.
The club cell and its protein, CC16: Time to shine
2013, The Lancet Respiratory MedicineClub cell protein (CC16) in serum as an effect marker for small airway epithelial damage caused by diesel exhaust and blasting fumes in potash mining
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Disclosure of potential conflict of interest: O. Michel, none disclosed; R. Murdoch is an employee of GlaxoSmithKline; A. Bernard, none disclosed.