EOSINOPHIL COLONY FORMING CELLS IN EOSINOPHILIC DISEASES

  • Butterfield, Joseph H (PI)

Project: Research project

Project Details

Description

Eosinophilia is characteristic of a variety of disease states ranging from
asthma and atopic dermatitis to parasitic infestations and the
hypereosinophilic syndrome (HES). The factors influencing stem cell
commitment to the eosinophil line and subsequent excessive
eosinophilopoiesis in these diseases are largely unexplored. Eosinophil
colony-forming cells (EO-CFC) are the predominant colony-forming cell in
normal peripheral blood, yet, circulating eosinophilis constitute only 1-3%
of the normal circulating leukocyte population. The significance of this
discrepancy and the role of circulating EO-CFC in production of tissue
eosinophilia have not been determined. Patients with HES are heterogeneous
in terms of their clinical presentations, level of blood eosinophilia and
their prognosis. In our proposed studies we will quantitate EO-CFC in bone
marrow and peripheral blood patients with HES and test their colony-forming
ability in response to exogenous and autologous sources of
colony-stimulating factor (CSF). Experiments on normal CFC will be
conducted to determine whether patients with HES produce excessive
quantities of EO-CSF. The ability of EO-CFC from HES patients to
proliferate semiautonomously will be tested by examination of their growth
potential under suboptimal culture conditions and by their ability to
reproduce features of HES when injected into nude mice. Next, we will
produce monoclonal antibody to EO-CFC using light density cell fractions
from eosinophil colonies grown in soft agar or mythylcellulose culture as
the immunogen. Monoclonal anti-EO-CFC will be screened for its reactivity
against mature eosinophils, polymorphonuclear cells, fibroblasts and
granulocyte-macrophage CFC. The antibody's ability to select EO-CFC from a
mixed population of cells will be determined utilizing fluorescence
activated cell sorting and soft agar culture of labeled and unlabeled
cells. Using a fluorescent antibody technique the monoclonal antibody will
be used as a probe to detect the presence of EO-CFC in tissues which
normally contain large numbers of eosinophils. Lastly, we will test the
ability of the monoclonal antibody both alone and when conjugated to ricin
chain-A to selectively kill normal and HES EO-CFC in vitro.
StatusFinished
Effective start/end date9/1/838/31/86

Funding

  • National Institutes of Health

ASJC

  • Medicine(all)
  • Immunology and Microbiology(all)

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