Influenza A virus induction of oxidative stress and MMP-9 is associated with severe lung pathology in a mouse model.
Infection by different strains of influenza virus presents different pictures. Whether the pathogenicity of influenza virus is defined by the ability of the virus to induce differential immunopathological responses in the lungs still remains unclear. We compared the immunopathological response induced by influenza virus A/WSN/33 (H1N1) and that by A/Panama-like (H3N2) virus in C57BL/6 mice. WSN virus, in contrast to Panama-like virus, induced high mortality and severe lung pathology accompanied by massive Gr-1(+) and CD11b(+) cell infiltration and high levels of CXCL6/GCP-2, CCL2/MCP-1 and TIMP-1 production. Infection by WSN virus but not by Panama-like virus induced up-regulation of the active and latent forms of MMP-9 in the lungs and MMP-2/9 inhibitor partially reduced WSN virus-induced lung pathology. Both Gr-1(+) and CD11b(+) cells in WSN virus-infected lungs produced reactive oxygen and nitrogen species (ROS/RNS). While wild type mice infected by WSN virus had severe lung pathology and the presence of oxidized phospholipids and numerous MMP-9(+) cells in the lungs, ncf1 deficiency ablated their expression and manifested less lung pathology. Employing a pulmonary mouse model we demonstrated in this study that infection by virulent influenza virus is characterized by a heavy cellular infiltration, severe lung pathology which is accompanied by oxidative stress and MMP-9 production.
Graduate Institute of Immunology, National Taiwan University College of Medicine, Taipei, Taiwan.
Yu-Hsiang
YH
Lee
Chia-Lin
CL
Lai
Chai-Lin
CL
Lai
Shih-Hung
SH
Hsieh
Chi-Chang
CC
Shieh
Li-Min
LM
Huang
Betty A
BA
Wu-Hsieh
D000818:Animals; D004195:Disease Models, Animal; D054884:Host-Pathogen Interactions; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology / Q000472:pathogenicity*; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology / Q000472:pathogenicity*; D008168:Lung / Q000473:pathology*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000473:pathology / Q000821:virology; D018384:Oxidative Stress; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D020780:Matrix Metalloproteinase 9
Influenza A virus; Lung pathology; MMP-9; Oxidative stress