Intracellular storage of surfactant and proinflammatory cytokines in co-cultured alveolar epithelium and macrophages in response to increasing CO2 and cyclic cell stretch.
Cell stretch stimulates both surfactant and cytokine production. The authors proposed that stretch, through these effects, modifies the pathogenesis of lipopolysaccharide-induced acute lung injury (ALI), and that this is CO(2) dependent. Rat alveolar type II cells and macrophages were co-cultured with lipopolysaccharide in 5%, 10%, or 20% CO(2) +/- stretch (30%, 60 cycles/min) for 6 hours. Intracellular TNF-alpha and IL-6 increased whereas secreted cytokine and surfactant decreased with increasing CO(2). Stretch independently increased intracellular TNF-alpha and decreased IL-6 secretion. Elevated CO(2) may therefore diminish secretion of proinflammatory cytokines by alveolar cells, contributing to an explanation for protective hypercapnia in ALI.
Dixon
Dani-Louise
DL
Department of Critical Care Medicine, Flinders University, Adelaide, SA 5006, Australia. dani.bryan@flinders.edu.au
Barr
Heather A
HA
Bersten
Andrew D
AD
Doyle
Ian R
IR
D000818:Animals; D002245:Carbon Dioxide / Q000494:pharmacology*; D002453:Cell Cycle; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism*; D004847:Epithelial Cells; D007249:Inflammation; D015850:Interleukin-6 / Q000096:biosynthesis / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000378:metabolism*; D051381:Rats; D012128:Respiratory Distress Syndrome / Q000209:etiology; D013314:Stress, Mechanical; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism
D016207:Cytokines; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011663:Pulmonary Surfactants; D014409:Tumor Necrosis Factor-alpha; D002245:Carbon Dioxide