# LEUKOCYTE RECEPTORS FOR ENDOTHELIUM

> **NIH NIH R01** · STANFORD UNIVERSITY · 1991 · $126,752

## Abstract

Our objective is to characterize the structure and function of leukocyte
surface molecules that mediate binding of circulating leukocytes to
endothelium, and to define their role in lymphocyte traffic and leukocyte
extravasation in sites of inflammation. 1) Functional properties of gp90
"homing receptors" will be defined at the molecular level: The ability of
affinity isolated gp90s to bind high endothelial cells will be tested
using artificial lipid membrane techniques: and their capacity to bind
vascular addressing, and to interact as lectins with PPME and related
carbohydrate inhibitors of HEV recognition, will be studied using
fluorescence energy transfer. 2) Antibody inhibition studies will be
carried out to determine whether the integrin-related adhesion molecules
LFA-1 and LPAM-1 are involved in lymphocyte binding to purified mucosal
addressing. 3) The cellular and molecular mechanisms responsible for
leukocyte-specific interactions with postcapillary venules (PCV) during
extravasation into inflammatory sites will be explored. Ex vivo assays of
leukocyte binding to PCV in frozen sections of inflamed tissues will
define the specificity of neutrophil, monocyte, and eosinophil binding to
endothelium during acute, chronic, and parasitic inflammation. Ex vivo
assays, intravital microscopic observations of blood-borne fluorescent-
labeled leukocytes interacting with inflamed PCV or HEV, and conventional
in vivo homing/localization studies will be used to explore the cellular
and molecular mechanisms involved in leukocyte-specific PCV interactions
(margination and rolling, adhesion, cementing of binding, diapedesis: and
inhibition of these events by antibodies to homing receptors, the Mac-
1/Lfa-1 family, and other adhesion molecules). 4) Anti-gp90 homing
receptor antibodies will be produced in an attempt to a) define variable,
function-associated epitopes on gp90 Mermes in the human b) identify
hypothesized gp90 mucosal homing receptors in the mouse; and c) define
common epitopes or domains on murine gp90 mucosal homing receptors in the
mouse; and c) define common epitopes or domains on murine gp90 homing
receptors of diverse specificities. 5) Ex vivo leukocyte-PCV binding and
in vivo assays will be used to assess the role of specific inflamed PCV
recognition in the traffic of activated T cells to delayed type
hypersensitivity and allograft sites. and of "gut homing" lymphocyte
subsets to the mucosal lamina propria. 6) The effects of IFN-gamma on
leukocyte expression of adhesion molecules in vivo, and on leukocyte
interactions with PCV in inflammatory sites will be explored to help
elucidate the mechanism or suppression of neutrophil infiltration into
inflammatory sites during systemic IFN-gamma treatment.

Preliminary studies demonstrate a critical role for tissue-and leukocyte
subset-specific recognition of PCV in leukocyte extravasation, and hence
in normal and pathologic inflammatory responses. The proposed studies
should further define the ...

## Key facts

- **NIH application ID:** 3129411
- **Project number:** 5R01AI019957-09
- **Recipient organization:** STANFORD UNIVERSITY
- **SAM.gov UEI:** HJD6G4D6TJY5
- **Principal Investigator:** EUGENE C BUTCHER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $126,752
- **Award type:** 5
- **Project period:** 1983-09-01 → 1994-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3129411

## Citation

> US National Institutes of Health, RePORTER application 3129411, LEUKOCYTE RECEPTORS FOR ENDOTHELIUM (5R01AI019957-09). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3129411. Licensed CC0.

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