Gene transfer for cytokine functional studies in the lung: the multifunctional role of GM-CSF in pulmonary inflammation.
Using adenoviral-mediated gene transfer techniques, the murine granulocyte-macrophage colony-stimulating factor (GM-CSF) transgene is efficiently targeted to and highly expressed by the respiratory epithelium of rat lung. This lung tissue-directed expression of GM-CSF induces accumulation of both eosinophils and macrophages at early stages and an irreversible fibrotic reaction at later stages. These tissue responses to GM-CSF appear to be distinct from those induced by other proinflammatory cytokines, interleukin (IL)-5, IL-6, macrophage inflammatory protein-2 (MIP-2), or RANTES overexpressed in the lung. These findings clearly demonstrate that GM-CSF is more than a hematopoietic cytokine in the lung and may play a pivotal role in the multiple pathological processes underlying numerous respiratory illnesses, including asthma. In this overview, the differences in tissue responses induced by GM-CSF and other individual cytokines are highlighted. In addition, the mechanisms by which GM-CSF and other individual cytokines are highlighted. In addition, the mechanisms by which GM-CSF contributes to the development of eosinophilia, macrophage granuloma, and fibrosis are discussed in conjunction with the recent findings from us and others.
Xing
Z
Z
Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
Braciak
T
T
Ohkawara
Y
Y
Sallenave
J M
JM
Foley
R
R
Sime
P J
PJ
Jordana
M
M
Graham
F L
FL
Gauldie
J
J
D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000502:physiology*; D018014:Gene Transfer Techniques; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000502:physiology*; D006801:Humans; D015848:Interleukin-5 / Q000502:physiology; D008168:Lung / Q000502:physiology*; D051379:Mice; D011014:Pneumonia / Q000503:physiopathology*; D051381:Rats
D016207:Cytokines; D015848:Interleukin-5; D016178:Granulocyte-Macrophage Colony-Stimulating Factor