Lung Inflammation Induced by Lipoteichoic Acid or Lipopolysaccharide in Humans

• Published in: American journal of respiratory and critical care medicine Vol. 178; no. 1; pp. 34 - 41
• Main Authors: Hoogerwerf, Jacobien J, de Vos, Alex F, Bresser, Paul, van der Zee, Jaring S, Pater, Jennie M, de Boer, Anita, Tanck, Michael, Lundell, Daniel L, Her-Jenh, Chung, Draing, Christian, von Aulock, Sonja, van der Poll, Tom
• Format: Journal Article Conference Proceeding
• Language: English
• Published: New York, NY Am Thoracic Soc 01.07.2008; American Lung Association; American Thoracic Society
• Subjects: Adult; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Bacteria; Biological and medical sciences; Blood coagulation. Blood cells; Bronchoalveolar Lavage Fluid - chemistry; Bronchoalveolar Lavage Fluid - cytology; Cytokines; Cytokines - metabolism; Dose-Response Relationship, Drug; Escherichia coli; Fundamental and applied biological sciences. Psychology; Gene Expression Profiling; Gram-negative bacteria; Gram-Positive Bacteria; Humans; Immune system; Inflammation; Intensive care medicine; Laboratories; Lavage; Lipopolysaccharides - immunology; Lipopolysaccharides - pharmacology; Lung - pathology; Macrophages, Alveolar - metabolism; Male; Medical sciences; Molecular and cellular biology; Mortality; Neutrophils; NMR; Nosocomial infections; Nuclear magnetic resonance; Pathogens; Platelet; Pneumonia; Pneumonia, Bacterial - immunology; Pneumonia, Bacterial - pathology; Proteins; Staphylococcus aureus; Teichoic Acids - immunology; Teichoic Acids - pharmacology; Toll-Like Receptor 2 - agonists; Toll-Like Receptor 4 - agonists; Tumor necrosis factor-TNF; United States > US; Human; gram-positive bacteria; Lung disease; Pneumonia; Intensive care; Respiratory disease; Gram positive bacteria; Toll-like receptor agonists; Lipopolysaccharide; Inflammation; Resuscitation
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.200708-1261OC

Recognition of pathogen-associated molecular patterns by Toll-like receptors (TLRs) is considered to be important for an appropriate immune response against pathogens that enter the lower airways. We studied the effects of two different TLR agonists relevant for respiratory infections in the human lung: lipoteichoic acid (LTA; TLR2 agonist, component of gram-positive bacteria) and lipopolysaccharide (LPS; TLR4-agonist, component of gram-negative bacteria). Fifteen healthy subjects were given LPS or LTA: by bronchoscope, sterile saline was instilled into a lung segment followed by instillation of LTA or LPS into the contralateral lung. After 6 hours, a bronchoalveolar lavage was performed and inflammatory parameters were determined. Isolated RNA from purified alveolar macrophages was analyzed by multiplex ligation-dependent probe amplification. In addition, spontaneous cytokine release by alveolar macrophages was measured. Marked differences were detected between LTA- and LPS-induced lung inflammation. Whereas both elicited neutrophil recruitment, only LPS instillation was associated with activation of neutrophils (CD11b surface expression, degranulation product levels) and consistent rises of chemo-/cytokine levels. Moreover, LPS but not LTA activated alveolar macrophages, as reflected by enhanced expression of 10 different mRNAs encoding proinflammatory mediators and increased spontaneous cytokine release upon incubation ex vivo. Remarkably, only LTA induced C5a release. This is the first study to report the in vivo effects of LTA in men and to compare inflammation induced by LTA and LPS in the human lung. Our data suggest that stimulation of TLR2 or TLR4 results in differential pulmonary inflammation, which may be of relevance for understanding pathogenic mechanisms at play during gram-positive and gram-negative respiratory tract infection.