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4ß7 Integrins by Monoclonal Antibodies or Ligands Enhances Survival of Human Eosinophils In Vitro1
*
Department of Medicine, University of Wisconsin, Madison, WI 53706; and
Department of Biological Sciences, St. Cloud State University, St. Cloud, MN 56301
Asthma is characterized by an airway inflammatory infiltrate that
is rich in eosinophilic leukocytes. Cellular fibronectin and VCAM-1,
ligands for 
4 integrins, are enriched in the fluid of
airways of allergic patients subjected to Ag challenge. We therefore
hypothesized that ligands of 4 integrins can promote
eosinophil survival independent of cell adhesion. Cellular fibronectin
and VCAM-1 increased viability of human peripheral blood eosinophil in
a dose- and time-dependant manner whether the ligand was coated on the
culture well or added to the medium at the beginning of the assay.
Eosinophils cultured with cellular fibronectin were not adherent to the
bottom of culture wells after 3 days. Treatment with mAb Fib 30 to
ß7, but not mAb P4C10 or TS2/16 to ß1,
increased eosinophil survival. The increased survival of eosinophils
incubated with Fib 30 was blocked by Fab fragments of another
anti-ß7 mAb, Fib 504. Eosinophils incubated with
soluble cellular fibronectin or mAb Fib 30 for 6 h demonstrated a
higher level of GM-CSF mRNA than eosinophils incubated with medium
alone. Addition of neutralizing mAb to GM-CSF during incubation, but
not mAbs to IL-3 or IL-5, reduced the enhancement of eosinophil
survival by soluble cellular fibronectin or mAb Fib 30 to control
levels. Thus, viability of eosinophils incubated with cellular
fibronectin or VCAM-1 is due to engagement, probably followed by
cross-linking, of 4ß7 by soluble ligand
(or mAb) that stimulates autocrine production of GM-CSF and promotes
eosinophil survival.
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