CD14-deficient mice are protected against lipopolysaccharide-induced cardiac inflammation and left ventricular dysfunction.
BACKGROUND
The molecular mechanisms responsible for sepsis-induced myocardial dysfunction remain undefined. CD14 mediates the inflammatory response to lipopolysaccharide (LPS) in various organs including the heart. In this study we investigated the role of CD14 in LPS-induced myocardial dysfunction in vivo.


RESULTS
Wild-type and CD14-deficient (CD14-D) mice were challenged with Escherichia coli LPS. Myocardial tumor necrosis factor, interleukin-1beta (IL-1beta), and NOS2 induction was measured before and 6 hours after LPS challenge. Echocardiographic parameters of left ventricular function were measured before and 6 hours after LPS administration. LPS challenge induced a significant increase in myocardial tumor necrosis factor and IL-1beta mRNA and protein expression in wild-type mice. In contrast, mRNA and protein levels for TNF and IL-1beta were significantly blunted in CD14-D mice. An increase in NOS2 protein was noted within 6 hours of LPS provocation only in the hearts of wild-type mice. This was associated with an increase in ventricular cGMP levels. Activation of nuclear factor-kappaB was observed within 30 minutes of LPS in the hearts of wild-type mice but not in CD14-D mice. In wild-type mice, LPS significantly decreased left ventricular fractional shortening, velocity of circumferential shortening, and dP/dt(max). LPS-treated CD14-D mice maintained normal cardiac function.


CONCLUSIONS
These results suggest that CD14 is important in mediating the proinflammatory response induced by LPS in the heart and that CD14 is necessary for the development of left ventricular dysfunction during LPS-induced shock in vivo.
Knuefermann
Pascal
P
Department of Medicine, Baylor College of Medicine, Houston, Tex, USA.
Nemoto
Shintaro
S
Misra
Arunima
A
Nozaki
Naoki
N
Defreitas
Gilberto
G
Goyert
Sanna M
SM
Carabello
Blase A
BA
Mann
Douglas L
DL
Vallejo
Jesus G
JG
D000818:Animals; D006152:Cyclic GMP / Q000096:biosynthesis; D005260:Female; D006352:Heart Ventricles / Q000000981:diagnostic imaging; D006439:Hemodynamics; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000502:physiology*; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000096:biosynthesis; D012772:Shock, Septic / Q000139:chemically induced / Q000150:complications* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics; D014463:Ultrasonography; D018487:Ventricular Dysfunction, Left / Q000276:immunology* / Q000503:physiopathology / Q000517:prevention & control
D007375:Interleukin-1; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D006152:Cyclic GMP