Wilson Teicha C, Bachurski Cindy J, Ikegami Machiko, Jobe Alan H, Kallapur Suhas G
Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Division of Pulmonary Biology, OH 45229, USA.
Pediatr Res. 2005 Dec;58(6):1204-9. doi: 10.1203/01.pdr.0000185269.93228.29.
Serum amyloid A (SAA), an acute phase reactant (APR) protein, is induced in liver during systemic inflammation. Serum amyloid A3 (SAA3), an isoform of SAA, is induced in both liver and extra hepatic sites in response to proinflammatory stimuli such as cytokines. Previously, we showed a modest increase in plasma cytokine levels in a preterm lamb model of lung injury. The study objective was to determine the relative contributions of lung and liver to the acute phase response during postnatal lung injury. Preterm (130d) and near term (141d) newborn lambs (term=150d) were randomized to either no ventilation (controls), ventilation+intratracheal (IT) endotoxin (endo) or ventilation+IT saline. A group of near term lambs were exposed to ventilation+IV endotoxin. In the lungs, ventilation alone increased SAA3 mRNA 3- and 13-fold while ventilation+IT endotoxin increased SAA3 mRNA 64 and 366-fold above controls in preterm and near term lambs, respectively. In the liver, SAA3 mRNA was induced by ventilation alone (three-fold) and ventilation+IT endotoxin (45-fold) above controls in both preterm and near term animals. Ventilation + IV endotoxin caused the highest increase in SAA3 mRNA (212-fold) in the liver of near term animals. A different isoform, identified as SAA-Liver inducible was maximally induced in liver by ventilation alone with minimal further response to endotoxin. Lung SAA3 mRNA expression was detected primarily in airway epithelium, bronchial glands, perichondrium of bronchial cartilage and vascular smooth muscle cells. Our experiments show rapid induction of an APR gene in lung in response to proinflammatory stimuli.
血清淀粉样蛋白A（SAA）是一种急性期反应蛋白（APR），在全身炎症期间由肝脏诱导产生。血清淀粉样蛋白A3（SAA3）是SAA的一种同种型，在肝脏和肝外部位均可因细胞因子等促炎刺激而被诱导产生。此前，我们在早产羔羊肺损伤模型中发现血浆细胞因子水平有适度升高。本研究的目的是确定出生后肺损伤期间肺和肝脏对急性期反应的相对贡献。将早产（130天）和近足月（141天）的新生羔羊（足月=150天）随机分为不进行通气（对照组）、通气+气管内（IT）内毒素（内毒素）或通气+IT生理盐水组。一组近足月羔羊接受通气+静脉内毒素处理。在肺中，仅通气就使SAA3 mRNA增加了3倍和13倍，而通气+IT内毒素分别使早产和近足月羔羊的SAA3 mRNA比对照组增加了64倍和366倍。在肝脏中，仅通气（3倍）和通气+IT内毒素（45倍）就使早产和近足月动物的SAA3 mRNA高于对照组。通气+静脉内毒素使近足月动物肝脏中的SAA3 mRNA增加最多（212倍）。另一种同种型，被鉴定为肝脏诱导型SAA，仅通气就能在肝脏中最大程度地诱导产生，对内毒素的进一步反应最小。肺SAA3 mRNA表达主要在气道上皮、支气管腺体、支气管软骨的软骨膜和血管平滑肌细胞中检测到。我们的实验表明，肺中APR基因可因促炎刺激而快速诱导产生。
