کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5932379 1573386 2014 15 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Regular articleImmunopathology and infectious diseasesImmunoneutralization of Endogenous Aminoprocalcitonin Attenuates Sepsis-Induced Acute Lung Injury and Mortality in Rats
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
Regular articleImmunopathology and infectious diseasesImmunoneutralization of Endogenous Aminoprocalcitonin Attenuates Sepsis-Induced Acute Lung Injury and Mortality in Rats
چکیده انگلیسی

Acute lung injury (ALI) secondary to sepsis is a complex syndrome associated with high morbidity and mortality. We report that aminoprocalcitonin (NPCT), an endogenous peptide derived from the prohormone procalcitonin, plays a critical role in the development of ALI during severe sepsis and is a suggested risk factor for sepsis morbidity and mortality. Lethal sepsis was induced in rats by cecal ligation and puncture (CLP). Two hours after CLP, an i.p. injection of 200 μg/kg of anti-rat NPCT antibody was followed by continuous infusion of anti-NPCT (16 μg per hour) via a minipump for 18 hours. Samples were harvested 20 hours after CLP. High expressions of the CALCA gene, procalcitonin, and NPCT were detected in the lung tissue of rats with severe sepsis. Immunoneutralization of NPCT decreased pulmonary levels of CALCA, procalcitonin, and NPCT; reduced lung inflammation and injury, neutrophil infiltration, and bacterial invasion; and improved survival in sepsis. Anti-NPCT treatment also suppressed sepsis-induced inflammatory cytokine expression, cytoplasmic degradation of the inhibitor of NF-κB, IκBα, and nuclear NF-κB translocation in lung tissues. Therapeutic benefits of anti-NPCT were also associated with increased pulmonary levels of the anti-inflammatory cytokine IL-10. These data support a pathogenic role for NPCT in sepsis and suggest NPCT as a potential new target for clinical prevention and treatment of ALI in severe sepsis.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The American Journal of Pathology - Volume 184, Issue 11, November 2014, Pages 3069-3083
نویسندگان
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