# MECHANISMS OF HUMAN BASOPHIL & MAST CELL DESENSITIZATION

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 1991 · $155,440

## Abstract

Basophil and mast cell mediator release is a central feature of
both acute and chronic allergic reactions.  However, little is
known of the biochemical nature of signal transduction in human
cells of this type.  This proposal focuses on studies which will
elucidate some of the important biochemical events in both IgE
mediated and univalent hormone induced secretion.  The primary
goal of these studies is to elucidate the mechanism of
desensitization although significant effort will also be applied
towards understanding activation events.  In particular, the role
of phospholipid metabolism and protein kinase C in activation and
desensitization will be examined.  we have recently demonstrated
that IgE-mediated histamine release in both basophils and lung
mast cells is accompanied by changes in phosphotidyinositol,
increased activity of membrane associated protein kinase C and
elevations in cytosolic calcium.  It appears that protein kinase C
activity increases (with IgE-mediated stimulation) even in the
absence of external calcium suggesting that this enzyme may also
play a role in the desensitization process of human basophils and
mast cells.  As such, we hypothesize that protein kinase C
phosphorylates a 5'-phosphomonoesterase which in turn becomes
active in metabolizing inositol trisphosphate to its inactive form.
Since inositol trisphosphate is currently hypothesized to mediate
elevations in cytosolic calcium this proposed scheme could
account for the phenomenon of desensitization.  To substantiate
this model of desensitization measurements will be made of
phospholipid turnover, in particular phosphotidyinositol, and the
two side products of phospholipase C activation, inositol
trisphosphate and diacylglercerol in an effort to delineate more
accurately their role in activation.  Studies will also involve
measurements of protein kinase C activation and determine which
proteins are phosphorylated by its activation, particularly under
calcium-free buffer conditions.  Phosphorylation of 5'-
phosphomonoesterase will be directly examined as will its activity
in desensitized basophils and mast cells.

## Key facts

- **NIH application ID:** 3129817
- **Project number:** 5R01AI020253-07
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **SAM.gov UEI:** FTMTDMBR29C7
- **Principal Investigator:** Donald W MacGlashan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $155,440
- **Award type:** 5
- **Project period:** 1984-12-01 → 1993-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3129817

## Citation

> US National Institutes of Health, RePORTER application 3129817, MECHANISMS OF HUMAN BASOPHIL & MAST CELL DESENSITIZATION (5R01AI020253-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3129817. Licensed CC0.

---

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