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Plus Fibronectin1
Department of Pathology and Laboratory Medicine, University of Wisconsin Medical School, Madison, WI 53792
Airway eosinophils show prolonged in vitro survival compared with
peripheral blood eosinophils (PBEos). Recent studies have shown that
autocrine production and release of GM-CSF is responsible for enhanced
survival, but the mechanisms controlling cytokine production remain
obscure. We compared GM-CSF mRNA decay in eosinophils from
bronchoalveolar lavage (BALEos) after allergen challenge or from PBEos.
BALEos showed prolonged survival in vitro (60% at 4 days) and
expressed GM-CSF mRNA. The enhanced survival of BALEos was 75%
inhibited at 6 days by neutralizing anti-GM-CSF Ab. Based on
transfection studies, GM-CSF mRNA was 2.5 times more stable in BALEos
than in control PBEos. Treatment of PBEos with fibronectin and TNF-
increased their in vitro survival, GM-CSF mRNA expression, and GM-CSF
mRNA stability to a comparable level as seen in BALEos. These data
suggest that TNF- plus fibronectin may increase eosinophil survival
in vivo by controlling GM-CSF production at a posttranscriptional
level.
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