Anti-Inflammatory Mechanisms of Apolipoprotein A-I Mimetic Peptide in Acute Respiratory Distress Syndrome Secondary to SepsisReportar como inadecuado




Anti-Inflammatory Mechanisms of Apolipoprotein A-I Mimetic Peptide in Acute Respiratory Distress Syndrome Secondary to Sepsis - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Acute respiratory distress syndrome ARDS due to sepsis has a high mortality rate with limited treatment options. High density lipoprotein HDL exerts innate protective effects in systemic inflammation. However, its role in ARDS has not been well studied. Peptides such as L-4F mimic the secondary structural features and functions of apolipoprotein apoA-I, the major protein component of HDL. We set out to measure changes in HDL in sepsis-mediated ARDS patients, and to study the potential of L-4F to prevent sepsis-mediated ARDS in a rodent model of lipopolysaccharide LPS-mediated acute lung injury, and a combination of primary human leukocytes and human ARDS serum. We also analyzed serum from non-lung disease intubated patients controls and sepsis-mediated ARDS patients. Compared to controls, ARDS demonstrates increased serum endotoxin and IL-6 levels, and decreased HDL, apoA-I and activity of anti-oxidant HDL-associated paraoxanase-1. L-4F inhibits the activation of isolated human leukocytes and neutrophils by ARDS serum and LPS in vitro. Further, L-4F decreased endotoxin activity and preserved anti-oxidant properties of HDL both in vitro and in vivo. In a rat model of severe endotoxemia, L-4F significantly decreased mortality and reduces lung and liver injury, even when administered 1 hour post LPS. Our study suggests the protective role of the apoA-I mimetic peptide L-4F in ARDS and gram-negative endotoxemia and warrant further clinical evaluation. The main protective mechanisms of L-4F are due to direct inhibition of endotoxin activity and preservation of HDL anti-oxidant activity.



Autor: Oleg F. Sharifov, Xin Xu, Amit Gaggar, William E. Grizzle, Vinod K. Mishra, Jaideep Honavar, Silvio H. Litovsky, Mayakonda N. Pal

Fuente: http://plos.srce.hr/



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