Stretch and CO2 modulate the inflammatory response of alveolar macrophages through independent changes in metabolic activity.
Ventilatory-induced strain can exacerbate acute lung injury (ALI). Current ventilation strategies favour low tidal volumes and high end-expiratory volumes to 'rest' the lung, but can lead to an increase in CO2. Alveolar macrophages (AM) play a pivotal role in ALI through the release of inflammatory mediators. The effect of physical strain and CO2 on the release of pro-inflammatory mediators was examined in isolated rat AM. AM were cultured on IgG-coated silastic membranes with or without lipopolysaccharide (LPS) and 5% or 20% CO2 and subjected to a repetitive sinusoidal mechanical strain (30%, 60 cycles/min) for 4 h. Cell viability and metabolic activity were assessed. In both the presence and absence of LPS, physical strain increased metabolic activity by approximately 5%, while 20% CO2 decreased metabolic activity by approximately 40%. Twenty per cent CO2 decreased TNF-alpha secretion by approximately 45%, without affecting cell viability. Physical strain enhanced LPS-induced secretion of TNF-alpha by 1.5%, but not IL-6 or CINC-1. Hence, the effects of both CO2 and physical strain are mediated independently through changes in AM metabolic activity. Physical strain is not a major determinant of TNF-alpha, IL-6 or CINC-1 in AM. Our results confirm that high CO2 can lessen the TNF-alpha inflammatory response of AM.
Lang
Carol J
CJ
Department of Human Physiology, Flinders University of South Australia, Bedford Park, SA 5042, Australia. carol.lang@adelaide.edu.au
Barnett
Emma K
EK
Doyle
Ian R
IR
D000818:Animals; D002245:Carbon Dioxide / Q000502:physiology*; D002474:Cell-Free System / Q000378:metabolism; D002478:Cells, Cultured; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical
D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D002245:Carbon Dioxide