# TRANSEPITHELIAL MIGRATION OF HUMAN NEUTROPHILS

> **NIH NIH R01** · SUNY DOWNSTATE MEDICAL CENTER · 1991 · $112,790

## Abstract

Neutrophils and monocytes initially accumulate in response to
influenza infection.  However, very little is known about how these
leukocytes are attracted to sites of viral infection, how they
recognize virus-infected cells, the effect they have on the course
of the viral infection or in maintaining the integrity of the
epithelium.  To address these issues an in vitro model of influenza
infection will be used.  How leukocytes are attracted to virus
infected epithelium (MDCK) will be determined.  The adherence of
human neutrophils and monocytes to infected epithelial cells (or
LLC-PK1 cells transfected with the hemagglutinin gene of
A/Japan/305/57(H2N2 and its inhibition with monoclonal antibodies
(mab) will be used to determine:  1) the ability of these
leukocytes to recognize virus-infected epithelial 2) the stage in
the replication cycle when this occurs and 3) if this binding is
to the viral hemagglutinin molecule expressed on the surface of
infected cells.  To examine if there is a relationship between
leukocyte viral binding molecules and other leukocyte adhesion-
promoting receptors (complement receptors CRl and CR3, and the
receptor for the Fc region of IgG (FcR)), mab to these receptors
will be used to inhibit neutrophil agglutination by influenza virus
and to form ligand-coated surfaces which will trap these receptors
on the adherent cell membrane of the leukocytes.  The ability of
virus to bind to the CRl, CR3 or FcR receptor-free surface will be
determined with (35S) methionine-labelled virus and by electron
microscopy.  The leukocyte molecules which bind influenza strain
WSN(HlNl) can also be redistributed to the adherent surface of the
leukocyte.  Using this methodology one can then examine if these
binding molecules are involved in the binding of other influenza
serotypes or other viruses.  The effect of leukocyte accumulation
on the progression of the viral infection and on the permeability
of the infected epithelium will be determined by continuous
transepithelial electrical resistance studies.  Finally, the effect
of leukocyte passage on the polarized distribution of virions and
endogenous and viral antigens in the epithelial cell membrane will
be determined by immunofluorescence and ultrastructural
immunocytochemistry.  The results of these studies should provide
insight into how leukocytes are attracted to and recognize
influenza-infected epithelia and the role they play in limiting
viral spread and initiating recovery.

## Key facts

- **NIH application ID:** 3126676
- **Project number:** 5R01AI016480-09
- **Recipient organization:** SUNY DOWNSTATE MEDICAL CENTER
- **SAM.gov UEI:** NJ14V2NZYM68
- **Principal Investigator:** EVA B CRAMER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $112,790
- **Award type:** 5
- **Project period:** 1980-02-01 → 1994-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3126676

## Citation

> US National Institutes of Health, RePORTER application 3126676, TRANSEPITHELIAL MIGRATION OF HUMAN NEUTROPHILS (5R01AI016480-09). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3126676. Licensed CC0.

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