Pulmonary and systemic induction of SAA3 after ventilation and endotoxin in preterm lambs.
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.
Wilson
Teicha C
TC
Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Division of Pulmonary Biology, OH 45229, USA.
Bachurski
Cindy J
CJ
Ikegami
Machiko
M
Jobe
Alan H
AH
Kallapur
Suhas G
SG
D000208:Acute Disease; D000818:Animals; D000831:Animals, Newborn; D004731:Endotoxins; D005260:Female; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008168:Lung / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D011014:Pneumonia / Q000139:chemically induced / Q000209:etiology / Q000378:metabolism*; D011247:Pregnancy; D047928:Premature Birth; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012123:Pulmonary Ventilation; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D012756:Sheep
D004731:Endotoxins; D020033:Protein Isoforms; D012333:RNA, Messenger; D000685:Serum Amyloid A Protein