# IN VITRO STUDIES OF HUMAN ANAPHYLAXIS

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 1991 · $399,823

## Abstract

The goal of this proposal is to understand allergic disease processes and,
in so doing, provide the means for the development of new modalities of
therapy. The in vitro portion of this work focuses upon isolated and, most
often, purified human basophils and mast cells. A major hypothesis of this
proposal is that understanding the biochemistries -- the signal
transduction mechanisms -- by which these cells secrete preformed and
newly generated mediators will eventually allow us to develop
pharmacologic agonists which block this release process. Several
biochemical processes will be studied, including protein kinase C
activation and changes in intercellular calcium concentrations; the role
of these processes will also be assessed with available pharmacologic
tools to evaluate their relationship to function. We will continue
experiments which suggest that agonists which increase intracellular cAMP
levels inhibit the production of arachidonic acid metabolites (LTC and
PGD) more effectively and via different pathways than they affect
histamine release. Function will also be evaluated in conjunction with
morphologic changes in collaboration with Dr. Ann Dvorak. It has recently
been appreciated that human mast cells are heterogeneous in terms of which
mediators are produced, which secretagogues are effective and in the
release mechanisms described above. We will study these parameters using
human lung, skin, gut, uterine and BAL mast cells and basophils. In vivo
mast cells and basophils function in the context of other cells; a major
goal of this proposal is to explore those interactions. We have described
a cytokine(s) coming from a variety of human cells which causes
IgE-dependent histamine release from basophils. These histamine releasing
factors (HRFS) are found in man in late phase reactions and their use has
revealed a functional heterogeneity of IgE -- only one type of IgE (IgE+)
can interact with HRF. We hypothesize that these cytokines play a major
role in inflammation and we would like to purify and clone a HRF, to
define the biochemical basis of IgE heterogeneity and to develop
immunoassays for HRF and IgE+. Finally, it is our goal to test the
relevance of the above studies in vivo in man. For this purpose, we are
characterizing the pattern of mediator release and cellular infiltration
after antigen challenge of the human upper and lower airways, skin and
conjunctiva. By the use of inhibitors and antagonists, it should be
possible to define which mediators and cells are most critically involved
in the pathogenesis of allergic inflammation.

## Key facts

- **NIH application ID:** 3124362
- **Project number:** 5R01AI007290-26
- **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:** 1991
- **Award amount:** $399,823
- **Award type:** 5
- **Project period:** 1975-06-01 → 1995-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3124362

## Citation

> US National Institutes of Health, RePORTER application 3124362, IN VITRO STUDIES OF HUMAN ANAPHYLAXIS (5R01AI007290-26). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3124362. Licensed CC0.

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