# RELATION OF GAMMA GLOBULIN STRUCTURE TO HYPERSENSITIVITY

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 1987 · $262,162

## Abstract

The purpose of this research project is to elucidate the biochemical
mechanisms of IgE-dependent mediator release from mast cells, which cause
allergic diseases.  Our efforts will be focused to analyze biochemical
events which are caused by the bridging of IgE-receptors on mast cells.
Recently, we established a culture system to obtain human basophilis in the
culture of the mononuclear cells in umbilical cord blood.  Cultured
basophils could be sensitized with human IgE for anti-IgE-induced histamine
release.  Thus, i) we shall identify growth factor(s) for human basophils
and characterize the cultured human basophils.  ii) Experiments will be
carried out to determine that membrane-associated enzymes, such as serine
protease and methyltransferase, are involved in the activation of cultured
basophils, and that this process will lead to Ca2+ uptake and mediator
release.  iii) The affinity of human IgE and rodent IgE for IgE-receptors
on cultured human basophilis will be determined, and iv) IgE-receptors on
the cells will be identified by SDS gel electrophoresis.  v) We shall
determine the substrate specificity of membrane-associated serine protease,
which is activated upon bridging of IgE receptors.  vi) Possible
relationship between the proteolytic enzyme and Alpha or Beta subunits of
IgE-receptors will be determined.  vii) The possibility is considered that
the activation of the protease results in the formation of a kinin-like
substance, which in turn activates the other membrane-associated enzymes
for mediator release.  We shall determine whether kallikrein-like enzymes
and/or bradykinin may induce the activation of methyltransferases and
adenylate cyclase in rodent mast cells and human basophils.  viii) The
possible role of phospholipid methylation in the enhancement of turnover of
phosphatidylinositol will be investigated by using rodent mast cells and
human cultured basophils.  ix) We shall analyze intracellular Ca2+ movement
and Ca++ influx into mast cells (basophils) induced by bridging of
IgE-receptors.  A fluorescent quinoline Ca++ indicator, Quin 2, will be
employed for the anlysis.  x) Finally, biochemical mechanisms of
desensitization will be investigated in mouse mast cells.  We shall test
the hypothesis that desensitization is due to activation of
membrane-associated enzymes, and that different enzymes are involved in the
activation of mast cells for mediator release and desensitization.  Similar
experiments on desensitization will be carried out with cultured human
basophils in future years.

## Key facts

- **NIH application ID:** 3124625
- **Project number:** 5R01AI010060-18
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **SAM.gov UEI:** FTMTDMBR29C7
- **Principal Investigator:** KIMISHIGE ISHIZAKA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $262,162
- **Award type:** 5
- **Project period:** 1974-09-01 → 1989-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3124625

## Citation

> US National Institutes of Health, RePORTER application 3124625, RELATION OF GAMMA GLOBULIN STRUCTURE TO HYPERSENSITIVITY (5R01AI010060-18). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3124625. Licensed CC0.

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