# Project 3- Role of Leukocyte-Platelet Interactions in Inflammation and Thrombosis

> **NIH NIH P01** · CLEVELAND CLINIC LERNER COM-CWRU · 2021 · $536,130

## Abstract

PROJECT SUMMARY/ABSTRACT
 This translational project will focus on systemic lupus erythematosus (SLE) as a unique disease model
of inflammation and thrombosis. SLE is a complex autoimmune disease. The prevalence of SLE ranges
from 20 to 150 cases per 100,000 population. SLE affects primarily women and there is a significant impact
of health disparities in patients with Lupus. SLE is 2-3 times more prevalent among African American and
Hispanic than among Caucasian women. Patients with SLE can experience significant symptoms, such as
chronic pain, extreme fatigue, hair loss, cognitive issues, and physical impairments that affect every facet
of their lives. Many suffer from cardiovascular disease, strokes, disfiguring rashes, and painful arthritis.
The 10-year survival rate is about 70%. Historically, SLE has been considered as an adaptive immune
system disorder characterized by the presence in patient serum of autoantibodies raised against nuclear
components which deposit in blood vessels, skin, kidney, lung, joints and brain causing tissue damage
and clinical manifestations. New advances in the understanding of SLE pathogenesis have focused on the
innate immune system, with a particular focus on leukocytes (i.e., neutrophils, monocytes) as key players
in perpetuating and amplifying this systemic disease. Currently, there is no prevention or cure for SLE, and
the mainstay of treatment is non-specific immunosuppressive and cytotoxic agents. Thus, there is
significant unmet clinical need in SLE and compelling demand for more effective therapeutic approaches.
Leukocyte-platelet interactions induce bidirectional signals that amplify pro-inflammatory and pro-
thrombotic cellular responses. We have focused on the leukocyte integrin Mac-1 (αMβ2), identifying this
adhesive receptor as a critical molecular determinant of leukocyte recruitment and signaling. Our
laboratory first reported the interaction between Mac-1 and its platelet counter-receptor GPIbα and
determined the molecular basis of GPIb recognition. We established that Mac-1:GPIbα broadly regulates
inflammation in models of vasculitis, glomerulonephritis, and multiple sclerosis as well as arterial
thrombosis. The central hypothesis of this proposal is that the Mac-1:GPIbα interaction is broadly required
for inflammation and initiates pro-inflammatory and prothrombotic signals that promote diverse disease
processes. The specific aims of the project are: 1) To determine the effect of disrupting Mac-1:GPIbα on
the progression and complications of SLE using mouse models; 2) To define the physical determinants of
Mac-1:GPIbα binding and the nature of “outside-in” signals generated by this interaction; and 3) To provide
evidence that clinical SLE disease activity is correlated with biomarkers of the Mac-1:GPIbα interaction.
Because leukocyte-platelet interactions broadly regulate inflammation and thrombosis, understanding the
molecular machinery of this cellular complex will provide important insights ...

## Key facts

- **NIH application ID:** 10268699
- **Project number:** 1P01HL154811-01A1
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** Daniel I Simon
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $536,130
- **Award type:** 1
- **Project period:** 2021-09-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10268699

## Citation

> US National Institutes of Health, RePORTER application 10268699, Project 3- Role of Leukocyte-Platelet Interactions in Inflammation and Thrombosis (1P01HL154811-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10268699. Licensed CC0.

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