Am. J. Respir. Cell Mol. Biol.,
Volume 18, Number 4, April, 1998 532-537
Visna-maedi Virus Induces Interleukin-8 in Sheep Alveolar Macrophages
through a Tyrosine-kinase Signaling Pathway
Isabelle
Legastelois,
Hélène
Levrey,
Timothy
Greenland,
Jean-François
Mornex,
and
Geneviève
Cordier
Laboratoire d'Immunologie et de Biologie Pulmonaire, Université Claude Bernard et Service de Pneumologie,
Hôpital Louis Pradel; and Laboratoire Associé de Recherches sur les Lentivirus chez les petits Ruminants,
INRA et Ecole Vétérinaire, Lyon, France
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-1
, and a possible rise in tumor necrosis factor 
(TNF) 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-1 and possibly of TNF
may explain the occurrence of a later persistent expression of IL-8 mRNA through an autocrine mechanism.
