# STUDY OF GAMMA GLOBULIN STRUCTURE AND HYPERSENSITIVITY

> **NIH NIH R01** · LA JOLLA INSTITUTE · 1990 · $215,039

## Abstract

(Adapted from applicant's abstract):  It has been established that IgE
molecules bind to Fc delta receptors on mast cells with high affinity, and
that cross linking of the cell bound IgE antibodies by antigen trigger the
cells for the release of mediators which cause allergic diseases.  The
purpose of this research project is to elucidate the immunological and
biochemical mechanisms of IgE-dependent mediator release.  Previous work
indicated that cross-linking of cell-bound IgE antibody molecules by
multivalent ligand induced activation of phospholipase C (PLC) for
hydrolysis of inositol phospholipids, and that this process may play a
major role in the transduction of triggering signals for mediator release.
In this proposal, i) the applicant shall study whether guanidine-
nucleotide binding protein(s) is involved in the IgE-mediated activation
of PLC and histamine release.  As the investigators have established the
method to permeabilize rat mast cells and bone marrow-derived mouse mast
cells (BMMC), the investigators shall introduce non-hydrolyzable GTP
analogue, such as GTP gammaS or GDPbetaS, into the permeabilized cells and
determine the effect of the GTP analogue, on antigen-induced hydrolysis of
inositol phospholipids and mediator release.  ii) The investigator's
recent experiment indicated that a newly synthesized inhibitor of
phospholipase A2 (PLA2) inhibited the antigen-induced histamine release
and arachidonic acid release from sensitized BMMC without affecting the
formation of inositol phosphates.  The investigators shall confirm that
the inhibitor does not affect the antigen-induced activation of PLC, and
determine whether the inhibitor may affect other enzymes involved in
phosphatidylinositol turnover.  The investigators expect that the
experiments will establish a possible role of PLA2 in IgE-dependent
mediator release.  iii) The investigators shall try to establish culture
conditions for selective differentiation and growth of human basophil
granulocytes and mast cells from umbilical cord blood cells and bone
marrow cells.  Recombinant interleukins from human T-cells or non-T-cells
will be employed.  Fibroblast monolayers will also be employed for the
differentiation of mast cells.  iv) The investigators shall also continue
their collaboration with molecular biologists to determine the binding
site on human IgE molecules to Fc delta receptors on basophils.
Recombinant peptides and synthetic peptides representing small segments of
the Fc portion of delta chain will be tested for the ability to block
passive sensitization of human basophils with IgE antibodies, and for the
ability to block the binding of 125 I-labeled IgE to Fc delta receptors on
cultured human basophils.

## Key facts

- **NIH application ID:** 3124622
- **Project number:** 2R01AI010060-20
- **Recipient organization:** LA JOLLA INSTITUTE
- **Principal Investigator:** KIMISHIGE ISHIZAKA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $215,039
- **Award type:** 2
- **Project period:** 1974-09-01 → 1992-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3124622

## Citation

> US National Institutes of Health, RePORTER application 3124622, STUDY OF GAMMA GLOBULIN STRUCTURE AND HYPERSENSITIVITY (2R01AI010060-20). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3124622. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*