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Objective To evaluate the potential effects of RS504393, CC chemokine receptor (CCR) 2b and CCR1 antagonist, on LPS-induced acute lung injury (ALI) and to investigate the underlying mechanisms. Method A549 cell line was stimulated with LPS (10 μg/mL) and then treated with RS504393 (10 μg/mL) for 6 hours. ALI model was established with intranasal administration of LPS (5 mg/kg) in C57BL/6J mice. RS504393 (5 mg/kg) was administered 30 min before LPS dripped nasally. IL-8, IL-1β, plasminogen activator inhibitor (PAI)-l,monocyte chemoattractant protein (MCP)-2,and the expressions of CCR1 and CCR2b were studied by using Realtime-RT-PCR, ELISA and cyto-flowmetry. Results In A549 cell line treated with RS504393,the expressions of CCR1, CCR2b and IL-8 were significantly inhibited after LPS stimulation. In rats with LPS-induced ALI, treatment with RS504393 significantly protected mice against lung injury by attenuating influx of leukocytes and protein into bronchoalveolar space and by lessening pathological changes of lung. Treatment with RS504393 down-regulated IL-1β and PAI-1 expressions in bronchoal veolar lavage fluid (BALF) and lungs at mRNA and protein levels along with up-regulation MCP-2 expression compared to rats of vehicle-treated groups. Conclusions CCR2b and CCR1 play pivotal roles in the development of ALl,and RS504393 as a antagonist can halt the development of ALI.
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Objective To investigate the changes in circulatory and pulmonary monary angiotensinⅡin rats with acite lung injury(ALI)and explore the role of angiotensinⅡin ALI.Method Thirty S-D rats were randomly divided into control group(n=6)and ALI group(n=24).The ALI group was further divided into four subgroups of observation at various intervals,3,6,9 and 12 hours after administration of lipopolysaccharide (LPS)into the femoral vein(each n=6).The indices rate,blood gas analysis,wet weight/dry weight(W/D)ratio of lung lobes,and pathological changes were successively observed at 3,6,9,and 12 hours after injury.The content of angiotensinⅡin lung tissue and blood plasma were detected at above set intervals by radioimmunoassay.Data of these assays were analyzed by one-factor analysis of variance.Results Compare with the control group,pH and PaO2 of arterial blood in ALI group decreased significantly(P＜0.05)at all intervals and PaCO2 of arterial blood in ALI group decreased significanfly(P＜0.05).at all intervals and PaCO2 of arterial blood and lung W/D weight ratio increased significantly(P＜0.05),and scores of lung histopathology denoted the lung injuried(P＜0.01).After injury of lung,angiotensin Ⅱ content increased markedly in lung homogenate and blood plasma (P＜0.05).Angiotensin Ⅱ content in blood plasma reached peak value at 9 hours,and content of angiotensin Ⅱ in lung homogenates kept on increasing at allintervals of observation.Conclusions A large amount of angiotensin Ⅱ releases into lung tissue and blood plasma during ALI,suggesting systemic and pulmonary rennin-angiotensin systems are activated.
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The macrophages exist in whole body tissues and maintain health condition and/or protect various diseases through appropriate their activations. We hypothesized that these macrophages formed network and this putative macrophages communication was termed a macrophage-network. Then to improve and/or maintain health status as far as possible, we focused on the some dietary-experienced Gram-negative bacteria with long experience of food production. We found a lipopolysaccharide (LPS) as macrophage-activating substances from water extract of wheat flour. This named it IP-PA1, immunopotentiator of <i>Pantoea agglomerans</i> which is the symbiotic Gram-negative bacteria of wheat.<br> While LPS is known as the strongest substance to activate macrophages, many people have prejudice against LPS as the toxin especially through intravenous route. Thus, nobody develop LPS as the medical drugs. Recently, the biological significance of LPS has been recognized as the regulator of homeostasis through signal transduction of TLR-4 in the body.<br> To apply the excellent function of LPS or LPS-containing materials for social health care, it is essential to investigate the basic science for the analysis of individual health maintenance system reevaluating biological significance of LPS based on the accumulation of scientific information about usefulness of LPS. To achieve these purposes, cooperation system with many specialists in different fields (university, industry, and government) should be needed.<br> Thus, we established an alliance composed of the, non profit organization (NPO) mainly for conduct of clinical trial with products containing LPS and evaluation of the various products in terms of both quality and quantity of LPS and its function, and university-led venture company mainly for transferring intellectual properties and for development and supply of new functional materials containing LPS derived from dietary-experienced Gram-negative bacteria including IP-PA1. In this manuscript, we introduce our concept for maintaining homeostasis based on the macrophage-network and processes in development of the product containing IP-PA1 which is a material from dietary-experienced Gram-negative bacteria to be applicable to health food.<br>