Visna-maedi virus induces interleukin-8 in sheep alveolar macrophages through a tyrosine-kinase signaling pathway.
The mechanisms leading to the severe lung damage seen in some sheep naturally infected with the visna-maedi virus, and to pulmonary lesions in other lentiviral diseases, appear to involve the recruitment of large numbers of uninfected inflammatory cells. Only a few alveolar macrophages from experimentally infected lambs express virus, but high levels of interleukin (IL)-8 mRNA are present in the macrophage population. In vitro infection with visna-maedi virus at low multiplicity of alveolar macrophages from uninfected sheep also strongly induced the expression of IL-8 mRNA and the accumulation of IL-8 in the extracellular medium. An initial peak of IL-8 mRNA expression at 3 or 6 h after infection was followed by a fall, then a more persistent expression lasting at least 48 h after infection. The early peak was accompanied by expression of mRNA for IL-1beta, and a possible rise in tumor necrosis factor alpha (TNFalpha) mRNA, although this was frequently elevated in uninfected ovine alveolar macrophages. Interestingly, these events occurred identically in cells treated with non-infectious heat-treated virus, suggesting that interaction between viral components and cellular membrane receptors could suffice for both early and late IL-8 induction. The level of IL-8 mRNA induced by treatment with live or inactivated virus could be severely reduced by pretreatment of the macrophages with genistein but not with staurosporine, suggesting the involvement of a tyrosine-kinase signaling pathway. The early induction of IL-1beta and possibly of TNFalpha may explain the occurrence of a later persistent expression of IL-8 mRNA through an autocrine mechanism.
Legastelois
I
I
Laboratoire d'Immunologie et de Biologie Pulmonaire, Université Claude Bernard et Service de Pneumologie, Hôpital Louis Pradel, Lyon, France.
Levrey
H
H
Greenland
T
T
Mornex
J F
JF
Cordier
G
G
D000818:Animals; D016207:Cytokines / Q000032:analysis / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D018836:Inflammation Mediators / Q000378:metabolism; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D016676:Macrophages, Alveolar / Q000737:chemistry / Q000378:metabolism* / Q000821:virology; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D012756:Sheep / Q000821:virology*; D015398:Signal Transduction; D013997:Time Factors; D016182:Visna / Q000503:physiopathology; D014790:Visna-maedi virus / Q000502:physiology*
D016207:Cytokines; D004791:Enzyme Inhibitors; D018836:Inflammation Mediators; D007375:Interleukin-1; D016209:Interleukin-8; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D019833:Genistein; D011505:Protein-Tyrosine Kinases