Delayed neutrophil apoptosis in sepsis is associated with maintenance of mitochondrial transmembrane potential and reduced caspase-9 activity*

作者：Ravi Taneja, Jean Parodo, Song Hui Jia, András Kapùs, Ori David Rotstein, John C. Marshall · 发表于：Critical Care Medicine · 年份：2004 · DOI：10.1097/01.ccm.0000129975.26905.77 · 被引用次数：228 · 研究领域：Immune Response and Inflammation、Cell death mechanisms and regulation、Neutrophil, Myeloperoxidase and Oxidative Mechanisms

OBJECTIVE: The resolution of neutrophil (PMN)-mediated inflammation occurs through the apoptosis, or programmed cell death, of the neutrophil. PMN apoptosis is inhibited by a variety of inflammatory stimuli; moreover, PMN from critically ill septic patients show profoundly delayed rates of apoptosis in vitro. Since apoptosis is effected through the activity of intracellular cysteine proteases (caspases), we evaluated caspase expression and activity in neutrophils from septic patients and compared them with caspase expression and activity of resting or lipopolysaccharide-activated neutrophils from healthy volunteers. DESIGN: Prospective observational cohort study. SETTING: Tertiary level intensive care unit and associated research laboratory. SUBJECTS: Thirty-six intensive care unit patients with sepsis; ten healthy laboratory controls. INTERVENTIONS: Collection of up to 10 mL of whole blood for in vitro study of rates of apoptosis, expression and activity of caspases-1, -3, and -9, activation of nuclear factor-kappaB, and change in mitochondrial transmembrane potential. MEASUREMENTS AND MAIN RESULTS: Following 24 hrs of in vitro culture, 52 +/- 7.8% of control neutrophils, but only 29 +/- 5.4% of lipopolysaccharide-stimulated (1 microg/mL) PMN, showed nuclear changes of apoptosis. Only 6.2 +/- 1.1% of neutrophils from septic patients were apoptotic after 24 hrs. Significant nuclear translocation of nuclear factor-kappaB was evident in septic PMN, and inhibition of apoptosis w...