Association between CD14 polymorphisms and serum soluble CD14 levels: effect of atopy and endotoxin inhalation.

BACKGROUND: A prerequisite for activation of the innate immune response by endotoxin is its binding to CD14. OBJECTIVE: The aim of this study was to evaluate the role of CD14 polymorphisms, atopy, and inhaled endotoxin in modulating serum CD14 levels. METHODS: Healthy volunteers (n = 88) were genotyped for CD14 polymorphisms at the -1619, -1359, and -159 loci, relative to the transcription start site. Subjects inhaled 20 mug of endotoxin, and white blood cell, C-reactive protein, LPS-binding protein, and soluble CD14 (sCD14) levels were measured before and after exposure. RESULTS: Homozygotes for the -1619G, -1359G, and -159T alleles had higher baseline levels of sCD14 than carriers of the CD14/-1619AA (P = .015), -1359GT/TT (P = .015), or -159CC (P = 0.017) genotypes. sCD14 levels increased within 24 hours of endotoxin inhalation (P < .0001 for all biomarkers); however, the association between CD14 polymorphisms and sCD14 levels was no longer present after exposure. The atopic status of an individual did not alter these associations. CD14 polymorphisms were not associated with levels of white blood cells, C-reactive protein, and LPS-binding protein before or after endotoxin challenge. CONCLUSION: These data suggest that CD14 promoter polymorphisms and inhaled endotoxin modulate sCD14 levels.

Work-related symptoms and inflammation among sewage plant operatives.

Sewage operatives at five sewage treatment plants (n = 59) and controls not exposed to sewage (n = 55) were examined to determine work-related symptoms and inflammatory responses. Symptoms were elicited using a questionnaire, and spirometry was performed. Inflammatory markers were determined in blood and nasal lavage. Workplace endotoxin and hydrogen sulfide were measured and adeno- and enterovirus antibodies were evaluated in blood. Gastrointestinal and airway symptoms, joint pains, unusual tiredness, and toxic pneumonitis were more common among operatives, and the proportion of blood neutrophils was higher among operatives as compared with controls. A relationship was found between several reported symptoms and the inflammatory markers. Hydrogen sulfide levels were very low. Endotoxin levels were generally low, but high at some work sites.

Measurement strategies for the determination of airborne bacterial endotoxin in sewage treatment plants.

Working in sewage plants can involve exposure to different types of microorganisms, viruses and chemicals. The purpose of this study was to evaluate different measurement strategies to determine airborne bacterial endotoxin in such plants. Sewage treatment plants in three municipalities in western Sweden were included. Measurements of airborne endotoxin were performed in April-May and September-October 2001 using personal and stationary samplers. The air sampling times ranged from 60 to 444 min. In stationary and personal sampler measurements, the amounts of airborne endotoxin detected were generally low. At specific worksites, however, higher endotoxin values were identified, with the highest values at worksites located indoors. The results suggest that the exposure situation is relatively stable over a short time period at a specific worksite and that higher values can be recorded during work practices where agitation of wastewater occurs. The results further suggest that airborne endotoxin exposure situations in sewage treatment plants are complex. Sampling techniques, indoor/outdoor measurements and identification of specific worksites/tasks where there is a risk of airborne endotoxin exposure are important factors that must be considered in order to obtain relevant exposure determinations and establish preventive measures from a health risk perspective.

Effects after inhalation of (1-->3)-beta-D-glucan and relation to mould exposure in the home.

BACKGROUND: Damp conditions indoors favour the growth of microorganisms, and these contain several agents that may cause inflammation when inhaled. Moulds contain a polyglucose in their cell wall, defined as (1-->3)-beta-D-glucan, exhibiting effects on inflammatory cells. AIM: The aim of the present study was to evaluate whether an inhalation challenge to purified (1-->3)-beta-D-glucan (grifolan) in humans could induce effects on inflammatory markers in blood, and to evaluate whether the reactions were related to the home exposure to (1-->3)-beta-D-glucan. METHODS: Seventeen subjects in homes with high levels of airborne (1-->3)-beta-D-glucan (G-high) and 18 subjects in homes with low levels of (1-->3)-beta-D-glucan (G-low) underwent two randomised, double-blind inhalation challenges, one to (1-->3)-beta-D-glucan suspended in saline and one to saline alone. A blood sample was taken before and after the challenges, and differential cell count, granulocyte enzymes in serum and the secretion of cytokines from peripheral blood mononuclear cells (PBMC) were measured. RESULTS: Inhalation challenge with (1-->3)-beta-D-glucan induced a decrease in the secretion of tumour necrosis factor alpha from endotoxin-stimulated PBMC in the G-high group as well as in the G-low group. In the G-high group, the inhalation of (1-->3)-beta-D-glucan induced an increase in blood lymphocytes that was significantly different from the saline-induced effect. CONCLUSIONS: The results suggest that an inhalation challenge to (1-->3)-beta-D-glucan has an effect on inflammatory cells and this effect may be related to a chronic exposure to moulds at home.

Mutations in the glycerol kinase gene restore the ability of a ptsGHI mutant of Bacillus subtilis to grow on glycerol.

Although glycerol is not taken up via the phosphotransferase system (PTS) in Bacillus subtilis, some mutations that affect the general components of the PTS impair the ability of cells to grow on glycerol. Five revertants of a pts deletion mutant that grow on glycerol were analysed. They were shown to carry mutations in the glycerol kinase gene. These are missense mutations located in parts of the glpK gene that could encode regions important for the activity of glycerol kinase. The results strongly suggest that the main effect of the PTS on glycerol utilization in B. subtilis is mediated via glycerol kinase.