Adenovirus type 7 induces interleukin-8 in a lung slice model and requires activation of Erk.
Adenovirus (Ad), particularly Ad type 7 (Ad7), causes severe lung infection and pneumonia. Initially, Ad causes neutrophilic inflammation of the distal airways and alveoli. Interleukin-8 (IL-8) is the major lung neutrophil chemotaxin, and we have shown that Ad7 induces IL-8 release from the A549 alveolar epithelial cell line. We sought to determine whether ex vivo human and bovine lung tissue containing primary pneumocytes could be used as a more accurate and relevant model to study Ad acute inflammation. We found that cultured lung tissue preserved normal lung architecture for more than 10 days. IL-8 was generated upon exposure of the lung organ culture to Ad7. IL-8 production required activation of the Ras/Erk pathway, since a pharmacological inhibitor blocked the appearance of IL-8 in the medium. Both human and bovine lung explants supported replication of Ad7, and immunohistochemistry experiments demonstrated the presence of the Ad hexon antigen within alveolar epithelial cells. These findings show that our novel human lung organ culture accurately reproduces the in vivo infectious disease process. Thus, this organ culture model represents a valuable tool for studying the acute innate immune response to respiratory infections.
Booth
J L
JL
Pulmonary and Critical Care Division, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA.
Coggeshall
K M
KM
Gordon
B E
BE
Metcalf
J P
JP
D000258:Adenovirus Infections, Human / Q000201:enzymology / Q000209:etiology / Q000276:immunology; D000260:Adenoviruses, Human / Q000145:classification / Q000472:pathogenicity*; D000818:Animals; D002417:Cattle; D002460:Cell Line; D046508:Culture Techniques; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000821:virology; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D008168:Lung / Q000201:enzymology / Q000276:immunology* / Q000821:virology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D010766:Phosphorylation; D011024:Pneumonia, Viral / Q000201:enzymology / Q000209:etiology / Q000276:immunology; D011650:Pulmonary Alveoli / Q000821:virology
D004791:Enzyme Inhibitors; D016209:Interleukin-8; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases