%0 Journal Article
%T Gadolinium Chloride Attenuates Sepsis-Induced Pulmonary Apoptosis and Acute Lung Injury
%A Osama A. Kishta
%A Peter Goldberg
%A Sabah N. A. Husain
%J ISRN Inflammation
%D 2012
%R 10.5402/2012/393481
%X Gadolinium chloride (GdCl3), a Kupffer cells inhibitor, attenuates acute lung injury; however, the mechanisms behind this effect are not completely elucidated. We tested the hypothesis that GdCl3 acts through the inhibition of lung parenchymal cellular apoptosis. Two groups of rats were injected intraperitoneally with saline or E. coli lipopolysaccharide. In two additional groups, rats were injected with GdCl3 24£¿hrs prior to saline or LPS administration. At 12£¿hrs, lung injury, inflammation, and apoptosis were studied. Lung water content, myeloperoxidase activity, pulmonary apoptosis and mRNA levels of interleukin-1¦Â, -2, -5, -6, -10 and TNF-¦Á rose significantly in LPS-injected animals. Pretreatment with GdCl3 significantly reduced LPS-induced elevation of pulmonary water content, myeloperoxidase activity, cleaved caspase-3 intensity, and attenuated pulmonary TUNEL-positive cells. GdCl3 pre-treatment upregulated IL-1¦Â, -2 and -10 pulmonary gene expression without significantly affecting the others. These results suggest that GdCl3 attenuates acute lung injury through its effects on pulmonary parenchymal apoptosis. 1. Introduction Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a frequent complication of sepsis affecting approximately from 25 to 40% of septic patients and carries a mortality of 40% [1]. Pathogenesis of sepsis-induced ALI proceeds through an early phase characterized by granulocyte migration inside capillaries and monocyte extravasation, an intermediate phase of monocyte differentiation into macrophages (M£¿s) inside alveoli, and a late phase of diffuse infiltration of alveoli by newly differentiated macrophages and extravasated neutrophils [2]. Recent studies have revealed that ALI is associated with enhanced apoptosis of pulmonary cells, including alveolar and airway epithelial cells as well as endothelial cells [3¨C5]. Inflammatory cell apoptosis is also enhanced in human with ARDS and in animal models of ALI [6]. The consequence of increased apoptosis in the lungs of septic patients is highly dependent on location of cellular apoptosis. While enhanced apoptosis of neutrophils and removal of apoptotic neutrophils by M£¿s can attenuate the extent of tissue injury induced by neutrophils, lymphocyte apoptosis is detrimental to the septic host [7]. Likewise, exaggerated apoptosis of pulmonary epithelial and endothelial cells is harmful and leads to a worsening of gas exchange abnormalities. Yet despite the increasing importance of pulmonary apoptosis as a major contributor to the pathogenesis of ALI, factors that
%U http://www.hindawi.com/journals/isrn.inflammation/2012/393481/