# IN VITRO STUDIES OF HUMAN ANAPHYLAXIS

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 1989 · $428,417

## Abstract

The aim of this grant is to understand human allergic disease processes
and, in so doing, to develop new means of therapy.  The in vitro portion of
this work focuses on purified human basophils and mast cells, the latter
obtained from lung and intestine.  We seek to understand the biochemical
mechanisms by which histamine and other mediators are released after
antigen or a-IgE challenge.  The studies involve measurements of
arachidonic acid metabolism and cyclic nucleotide levels in stimulated
cells with the aim of linking these metabolic events with mediator release
both kinetically and by studies with appropriate pharmacologic inhibitors.
Other nonimmune, but biologically relevant, stimuli (e.g., f-met peptides,
C5a, hyperosmolarity) also release mediators and the mechanisms of release
by these agents will be pursued.  We shall develop morphologic evidence
relating to the mechanisms of degranulation at the EM level.  We are
interested in defining the full panoply of mast cell and basophil
mediators, including arachidonic acid metabolites (LTC, PGD, 5HETE, etc.),
AGEPC, as yet undefined chemotactic factors, proteoglycans, and the
proteolytic enzymes capable of generating biologically active substances
such as kinins.  We shall study the importance, for allergic phenomena, of
basophil and mast cell interactions with eosinophils, platelets and
macrophages, each of which has variably well-defined factors which cause
mediator release.  We have observed that certain individuals have basophils
which are hyperresponsive to certain stimuli; this is often the case with
cells from atopics and usually the case with asthmatic individuals.  We
plan studies to understand the nature of this increased "releasability" and
its relationship to clinical disease.  The in vivo aspects of this project
involve nasal antigen challenge of sensitive individauls in the correlation
of clinical symptoms with measurement of mediators released in vivo
immediately after challenge and during the late phase reaction.  We shall
also study nonimmunologic stimuli in this system, focusing on release by
cold, dry air, a model for the airways response which is linked to
exercise-induced asthma.  Finally, we will study standard and novel drugs
to ascertain the relevance of in vitro inhibition of mediator release to
the in vivo results.  By understanding the patterns of mediator release and
the mechanisms by which it occurs with IgE-related and other stimuli, we
feel that clinically useful pharmacologic intervention in asthma and other
allergic diseases will become possible.

## Key facts

- **NIH application ID:** 3124361
- **Project number:** 5R01AI007290-24
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **SAM.gov UEI:** FTMTDMBR29C7
- **Principal Investigator:** LAWRENCE M LICHTENSTEIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $428,417
- **Award type:** 5
- **Project period:** 1975-06-01 → 1990-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3124361

## Citation

> US National Institutes of Health, RePORTER application 3124361, IN VITRO STUDIES OF HUMAN ANAPHYLAXIS (5R01AI007290-24). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3124361. Licensed CC0.

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