title: Reduced interferon-gamma secretion by natural killer cells from rats susceptible to postviral chronic airway dysfunction.
abstract: 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 (P < 0.005), 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 (P < 0.001). 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 (P < 0.05). 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 (P < 0.05). Therefore, reduced IFN-gamma secretion by NK cells in BN weanlings may play a role in the development of postviral chronic airway dysfunction.
authors.affiliation: Division of Allergy, Departments of Medicine and Pediatrics, and School of Pharmacy, University of Wisconsin, Madison, Wisconsin 53792, USA.
authors.forename: L D
authors.initials: LD
authors.lastname: Mikus
authors.forename: L A
authors.initials: LA
authors.lastname: Rosenthal
authors.forename: R L
authors.initials: RL
authors.lastname: Sorkness
authors.forename: R F
authors.initials: RF
authors.lastname: Lemanske
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D004198:Disease Susceptibility / Q000276:immunology / Q000378:metabolism; D016898:Interferon-alpha / Q000494:pharmacology; D007371:Interferon-gamma / Q000032:analysis / Q000378:metabolism*; D018664:Interleukin-12 / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology; D020382:Interleukin-18 / Q000494:pharmacology; D053614:Janus Kinase 2; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D007958:Leukocyte Count; D008173:Lung Diseases, Obstructive / Q000276:immunology* / Q000821:virology; D008297:Male; D010766:Phosphorylation; D014176:Protein Biosynthesis; D020033:Protein Isoforms / Q000096:biosynthesis; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis; D011518:Proto-Oncogene Proteins; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D018123:Receptors, Interleukin / Q000096:biosynthesis; D053707:Receptors, Interleukin-12; D018108:Respirovirus / Q000276:immunology; D010253:Respirovirus Infections / Q000276:immunology*; D050797:STAT4 Transcription Factor; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000821:virology; D013601:T-Lymphocytes / Q000166:cytology; D053634:TYK2 Kinase; D015534:Trans-Activators / Q000096:biosynthesis
chemical_list: D004268:DNA-Binding Proteins; C508444:Il12rb2 protein, rat; D016898:Interferon-alpha; D020382:Interleukin-18; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D050797:STAT4 Transcription Factor; D015534:Trans-Activators; D018664:Interleukin-12; D007371:Interferon-gamma; D011505:Protein-Tyrosine Kinases; C507927:Jak2 protein, rat; D053614:Janus Kinase 2; D053634:TYK2 Kinase; C499357:Tyk2 protein, rat