# LEUKOCYTE RECEPTORS FOR ENDOTHELIUM

> **NIH NIH R01** · STANFORD UNIVERSITY · 1987 · $183,667

## Abstract

Our objective is to characterize leukocyte surface receptors for
endothelium (LRE), and to define their role in lymphocyte traffic and
leukocyte extravasation in sites of inflammation.  1) We will examine the
expression of LRE by defined human lymphocyte subsets using a) a functional
in vitro assay of lymphocyte binding to high endothelial venules (HEV,
specialized venules that mediate the migration of lymphocytes from the
blood); and b) FACS analyses of cells stained with a monoclonal antibody
(Hermes-1) against human LRE.  2) Human lymphocyte LRE will be
characterized structurally in immunoprecipitation/gel analyses, and
functionally by their mimicry of or their effect on lymphocyte-HEV
interaction in vitro.  3) We have found that mouse neutrophils utilize
molecules similar if not identical to lymphocyte LRE to interact with
endothelial cells in vitro (in the frozen section model) and in vivo during
migration into acute inflammatory sites.  By using fluorescence and
immunoprecipitation analyses with Hermes-1 and MEL-14 (anti-mouse
lymphocyte receptor for lymph node HEV), in combination with functional in
vitro assays of binding to endothelial cells, we will ask whether
monocytes, natural killer cells (LGL), mast cells and other leukocytes (or
cell lines) utilize similar molecules to interact with endothelium.  FACS
analyses will be used to study the regulation of LRE during leukocyte
maturation, differentiation, and activation.  4) To understand the
site-specific extravasation of neutrophils versus lymphocytes, we will a)
explore the role of leukocyte and/or endothelial cell activation in
lymphocyte and neutrophil interactions with endothelium; b) study
functionally defined factor(s) that enhance lymphocyte-HEV interaction; and
c) seek structural and functional differences between lymphocyte and
neutrophil LRE.  5) To define mechanisms controlling lymphocyte traffic
into inflamed extralymphoid tissues, we will use in vitro and in vivo
assays to examine the function and specificity of HEV in sites of chronic
inflammation in pathologic specimens (inflamed skin, rheumatoid synovium)
and in CFA-induced granulomas in mice.  Preliminary studies indicate that a
novel receptor class (distinct from organ-specific receptor systems
operating in lymph nodes and mucosal lymphoid tissues) may direct
lymphocyte traffic into inflamed synovium, if so we will attempt to define
these receptors by producing monoclonal antibodies capable of blocking
lymphocyte interactions with synovial HEV.

These studies will improve our understanding of normal and pathologic
inflammatory responses.  They have the potential to lead to site-selective
means for controlling localized inflammatory/autoimmune disease processes.
In addition, they may shed light on molecular and evolutionary aspects of
cell-cell recognition mechanisms in other interacting cellular systems.

## Key facts

- **NIH application ID:** 3129408
- **Project number:** 5R01AI019957-05
- **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:** 1987
- **Award amount:** $183,667
- **Award type:** 5
- **Project period:** 1983-09-01 → 1989-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3129408

## Citation

> US National Institutes of Health, RePORTER application 3129408, LEUKOCYTE RECEPTORS FOR ENDOTHELIUM (5R01AI019957-05). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3129408. Licensed CC0.

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