Reduced interferon-gamma secretion by natural killer cells from rats susceptible to postviral chronic airway dysfunction
Autor: | Louis A. Rosenthal, Lance D. Mikus, Ronald L. Sorkness, Robert F. Lemanske |
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Rok vydání: | 2001 |
Předmět: |
Male
T-Lymphocytes Clinical Biochemistry Stimulation Leukocyte Count Interferon Rats Inbred BN Protein Isoforms Phosphorylation Cells Cultured Interleukin-18 Receptors Interleukin-12 Interleukin Protein-Tyrosine Kinases STAT4 Transcription Factor Interleukin-12 Sendai virus Specific Pathogen-Free Organisms DNA-Binding Proteins Killer Cells Natural medicine.anatomical_structure Disease Susceptibility Bronchoalveolar Lavage Fluid medicine.drug Pulmonary and Respiratory Medicine Spleen Biology Respirovirus Infections Virus Respirovirus Interferon-gamma Proto-Oncogene Proteins medicine Splenocyte Animals Secretion Lung Diseases Obstructive Molecular Biology TYK2 Kinase Interferon-alpha Cell Biology Receptors Interleukin Janus Kinase 2 biology.organism_classification Rats Inbred F344 Rats Protein Biosynthesis Immunology Trans-Activators |
Zdroj: | American journal of respiratory cell and molecular biology. 24(1) |
ISSN: | 1044-1549 |
Popis: | After parainfluenza type 1 (Sendai) virus infection as weanlings, Brown Norway (BN), unlike Fischer 344 (F344), rats develop an asthma-like phenotype. Reduced postinfection interferon (IFN)-gamma levels in bronchoalveolar lavage fluid from BN weanlings and the prevention of chronic airway sequelae in BN rats by IFN-gamma treatment led to the hypothesis that cells from BN weanlings have a reduced ability to secrete IFN-gamma. After stimulation with Sendai virus or interleukin (IL)-12, splenocytes from uninfected BN weanlings secreted significantly less IFN-gamma than did splenocytes from F344 weanlings (P0.005), as determined by enzyme-linked immunosorbent assay. Because levels of potential IFN-gamma-secreting cells in the spleen differed between the strains, natural killer (NK) cells, an important IFN-gamma source during early antiviral responses, were purified from spleens of uninfected weanlings. When stimulated with IL-12, BN NK cells secreted significantly less IFN-gamma than did F344 NK cells (P0.001). Incubation of NK cells from either strain with IL-12 and IL-18 resulted in synergistic increases in IFN-gamma production, but BN cells still secreted significantly less IFN-gamma than did F344 cells (P0.05). Similarly, after incubation with either IFN-alpha or IFN-alpha plus IL-18, BN NK cells secreted significantly less IFN-gamma than did F344 NK cells (P0.05). Therefore, reduced IFN-gamma secretion by NK cells in BN weanlings may play a role in the development of postviral chronic airway dysfunction. |
Databáze: | OpenAIRE |
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