lipoteichoic-acid and Lung-Diseases

The aims of the present study were to investigate the expression of Toll-like receptor (TLR)2 on the peripheral blood monocytes of patients with nontuberculous mycobacterial (NTM) lung disease and healthy controls, and to assess the responses of these monocytes to TLR2 agonists such as Mycobacterium avium and lipoteichoic acid (LTA). Reverse transcriptase-PCR was used to analyse TLR2 mRNA expression in peripheral blood monocytes from 17 NTM patients and 10 healthy controls. mRNA and protein secretion levels were also determined for the cytokines interleukin (IL)-12 p40 and tumour necrosis factor (TNF)-alpha. Expression of TLR2 mRNA by peripheral blood monocytes after stimulation with M. avium or LTA was lower in NTM patients than in healthy controls. IL-12 p40 and TNF-alpha mRNA and cytokine secretion levels were also lower in patients than in healthy controls. Treatment with anti-TLR antibody decreased M. avium- and LTA-induced IL-12 p40 and TNF-alpha production in healthy controls, but not in NTM patients. The present results suggest that the downregulation of Toll-like receptor 2 and the resulting decreased production of interleukin-12 p40 and tumour necrosis factor-alpha following Mycobacterium avium or lipoteichoic acid stimulation may contribute to host susceptibility to nontuberculous mycobacterial lung disease.

Topics: Cytokines; Female; Gene Expression Regulation; Genetic Predisposition to Disease; Humans; Interleukin-12 Subunit p40; Lipopolysaccharides; Lung Diseases; Male; Middle Aged; Monocytes; Mycobacterium avium; Mycobacterium Infections; RNA, Messenger; Teichoic Acids; Time Factors; Toll-Like Receptor 2; Tumor Necrosis Factor-alpha

Cell adhesion molecule expression (CAM) and IL-8 release in lung microvascular endothelium facilitate neutrophil accumulation in the lung. This study investigated the effects of lipoteichoic acid (LTA), a cell wall component of Gram-positive bacteria, alone and with LPS or TNF-alpha, on CAM expression and IL-8 release in human lung microvascular endothelial cells (HLMVEC). The concentration-dependent effects of Staphylococcus aureus (S. aureus) LTA (0.3-30 microg/ml) on ICAM-1 and E-selectin expression and IL-8 release were bell shaped. Streptococcus pyogenes (S. pyogenes) LTA had no effect on CAM expression, but caused a concentration-dependent increase in IL-8 release. S. aureus and S. pyogenes LTA (30 microg/ml) abolished LPS-induced CAM expression, and S. aureus LTA reduced LPS-induced IL-8 release. In contrast, the effects of S. aureus LTA with TNF-alpha on CAM expression and IL-8 release were additive. Inhibitory effects of LTA were not due to decreased HLMVEC viability, as assessed by ethidium homodimer-1 uptake. Changes in neutrophil adhesion to HLMVEC paralleled changes in CAM expression. Using RT-PCR to assess mRNA levels, S. aureus LTA (3 microg/ml) caused a protein synthesis-dependent reduction (75%) in LPS-induced IL-8 mRNA and decreased the IL-8 mRNA half-life from >6 h with LPS to approximately 2 h. These results suggest that mechanisms exist to prevent excessive endothelial cell activation in the presence of high concentrations of bacterial products. However, inhibition of HLMVEC CAM expression and IL-8 release ultimately may contribute to decreased neutrophil accumulation, persistence of bacteria in the lung, and increased severity of infection.

Topics: Cell Adhesion Molecules; Drug Interactions; E-Selectin; Endothelium, Vascular; Half-Life; Humans; Intercellular Adhesion Molecule-1; Interleukin-8; Lipopolysaccharides; Lung; Lung Diseases; Microcirculation; Neutrophil Infiltration; RNA Stability; RNA, Messenger; Sepsis; Streptococcus; Streptococcus pyogenes; Teichoic Acids; Tumor Necrosis Factor-alpha

Regimens of intravenous injections of saline-washed Lactobacillus fermentum elicited hypersensitivity reactions in rabbits. Pathological investigation revealed evidence consistent with induction of aggregate anaphylaxis, characterised by acute cor pulmonale. Additional evidence of similar tissue injury was observed in livers of rabbits which had received several intravenous injections of L. fermentum. Deposition of immune complexes in kidney glomeruli was demonstrated in only 1 out of 11 animals. Skin testing experiments revealed that lipoteichoic acid was involved in type I and type II antibody-mediated hypersensitive states. The involvement of bacterial cell surface components and extracellular products in such reactions implies a potential role in host tissue injury.

Topics: Animals; Hypersensitivity; Kidney Glomerulus; Lactobacillus; Lipopolysaccharides; Liver Diseases; Lung Diseases; Male; Phosphatidic Acids; Rabbits; Teichoic Acids; Vasculitis