Granulocyte macrophage colony stimulating factor is elevated in alveolar macrophages from sheep naturally infected with maedi-visna virus and stimulates maedi-visna virus replication in macrophages in vitro.
Infection by maedi-visna virus, a lentivirus of sheep, leads to chronic inflammatory reactions of various tissues. In this report we have analysed the role of specific cytokines in the disease process. A significant increase in expression of interleukin-6, interleukin-10, granulocyte macrophage-colony stimulating factor (GM-CSF) and transforming growth factor-beta1 mRNA was observed in alveolar macrophages isolated from the lungs of naturally infected animals when compared with lungs of seronegative controls. Levels of GM-CSF mRNA expression in alveolar macrophages correlated with the presence of lung lesions, but there was no correlation of interleukin-10, interleukin-6, tumour necrosis factor-alpha and transforming growth factor-beta1 mRNA levels in alveolar macrophages from animals with pulmonary lesions. In vitro investigation showed that GM-CSF in the range 0.1-10 ng/ml induced a significant increase in viral p25 production after 7 days in acutely infected blood monocyte-derived macrophages. The production of p25 peaked between 7 and 14 days exposure to 10 ng/ml of GM-CSF. Quantitative polymerase chain reaction showed that the level of viral DNA in monocyte-derived macrophages was dose-dependent following GM-CSF treatment in the range 0.1-100 ng/ml after 7 days. Viral mRNA expression was also enhanced. These findings indicate a role for GM-CSF in the pathogenesis of lymphoid interstitial pneumonia in infected animals.
Zhang
Z
Z
Department of Veterinary Pathology, University of Edinburgh, Edinburgh, UK. Zhidong.Zhang@bbsrc.ac.uk
Harkiss
G D
GD
Hopkins
J
J
Woodall
C J
CJ
D000818:Animals; D016207:Cytokines / Q000235:genetics; D004279:DNA, Viral / Q000378:metabolism; D015870:Gene Expression; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D066298:In Vitro Techniques; D016676:Macrophages, Alveolar / Q000378:metabolism* / Q000821:virology*; D011021:Pneumonia, Progressive Interstitial, of Sheep / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000821:virology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D012756:Sheep; D014764:Viral Proteins / Q000096:biosynthesis; D014779:Virus Replication / Q000187:drug effects; D014790:Visna-maedi virus / Q000187:drug effects* / Q000502:physiology*
D016207:Cytokines; D004279:DNA, Viral; D012333:RNA, Messenger; D012367:RNA, Viral; D011994:Recombinant Proteins; D014764:Viral Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor