# MECHANISMS OF VIRUS INDUCED ASTHMA

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 1988 · $165,529

## Abstract

Viral, not bacterial, symptomatic upper respiratory infections (URI)
frequently provoke attacks of asthma.  It was previously proposed that a
major mechanism in this relationship was an alteration in cell permeability
to calcium, a hypothesis subsequently supported by preliminary studies with
human leukocytes and the parainfluenza 3 (P-3) infected guinea pigs.  It is
now proposed to further determine whether or not respiratory viruses, or
their symptomatic infection, enhance the rise in cystolic Ca2+ that follows
cell activation, the consequence of which would lead to increased secretion
of spasmogenic mediators, generation of inflammatory bronchial injury, and
contraction of airway smooth muscle.  To establish this hypothesis,
selected calcium-dependent metabolic activities, estimates of cytoplasmic
free Ca2+ by the fluorescent indicator Quin 2 and phosphatidylinosital
bisphophate hydrolysis will be evaluated in human polymorphonuclear
leukocytes and basophils which have been either incubated in vitro with
influenza A virus or isolated from experimentally infected rhinovirus
patients showing airway hyperreactivity.  Human leukocytes have provided an
in vitro model to monitor virus effects on selected metabolic activity.
The initial studies will be conducted with PMNs and results from these will
serve as guides to selected analysis with isolated human basophils.  In P-3
infected guinea pigs, the calcium-dependency of airway smooth muscle and
its response to substance P will be determined along with studies of
basophils and pulmonary mast cells from the P-3 infected guinea pig to
establish abnormalities in calcium metabolism.  The P-3 infected guinea pig
has shown parallel changes in airway reactivity to humans with viral
respiratory infections and provides a unique opportunity to precisely
analyze in vivo pulmonary function subsequent isolated airway
responsiveness.  Furthermore, we have developed methods to isolate from the
guinea pig purified peripheral blood basophils and pulmonary mast cells.
Because the sequelae of viral respiratory infections is important not only
to asthma but other forms of lung disease, these studies are important to
our understanding and treatment of various forms of lung disease.

## Key facts

- **NIH application ID:** 3126356
- **Project number:** 5R01AI015685-09
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **SAM.gov UEI:** LCLSJAGTNZQ7
- **Principal Investigator:** William W. Busse
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $165,529
- **Award type:** 5
- **Project period:** 1979-06-01 → 1989-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3126356

## Citation

> US National Institutes of Health, RePORTER application 3126356, MECHANISMS OF VIRUS INDUCED ASTHMA (5R01AI015685-09). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3126356. Licensed CC0.

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