Xf. Lei et al., COMPARTMENTALIZED TRANSGENE EXPRESSION OF GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR (GM-CSF) IN MOUSE LUNG ENHANCES ALLERGIC AIRWAYSINFLAMMATION, Clinical and experimental immunology, 113(2), 1998, pp. 157-165
To investigate the role of GM-CSF in asthmatic airways inflammation, w
e have targeted GM-CSF transgene to the airway cells in a mouse model
of ovalbumin (OVA)-induced allergic airways inflammation, a model in w
hich there is marked induction of endogenous IL-5 and IL-4 but not GMC
SF. Following intranasal delivery of a replication-deficient adenovira
l gene transfer vector (Ad), transgene expression was found localized
primarily to the respiratory epithelial cells. Intranasal delivery of
0.03 x 10(9) plaque-forming units (PFU) of AdGM-CSF into naive BALB/c
mice resulted in prolonged and compartmentalized release of GM-CSF tra
nsgene protein with a peak concentration of approximate to 80 pg/ml de
tected in bronchoalveolar lava,ae fluid (BALF) at day 7, but little in
serum. These levels of local GMCSF expression per se resulted in no e
osinophilia and only a minimum of tissue inflammatory responses in the
lung of naive mice, similar to those induced by the control vector. H
owever, such GM-CSF expression in the airways of OVA sensitized mice r
esulted in a much greater and sustained accumulation of various inflam
matory cell types, most noticeably eosinophils, both in BALF and airwa
y tissues for 15-21 days post-OVA aerosol challenge, at which times ai
rways inflammation had largely resolved in control mice. While the lev
els of IL-5 and IL-4 in BALF and the rate of eosinophil apoptosis were
found similar between different treatments, there was an increased nu
mber of proliferative leucocytes in the lung receiving GM-CSF gene tra
nsfer. Our results thus provide direct experimental evidence that GM-C
SF can significantly contribute to the development of allergic airways
inflammation through potentiating and prolonging inflammatory infiltr
ation induced by cytokines such as IL-5 and IL-4.