# Novel mechanisms of platelet modified monocyte phenotype

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 2021 · $464,364

## Abstract

Summary
 Platelet interactions with immune cells – both direct and indirect – accelerate the pathogenesis of
vascular inflammatory and infectious diseases. Stimulated platelets release numerous immune molecules that
drive inflammation independent of any thrombotic functions. We have discovered a novel mechanism of
platelet initiated innate immune cell responses; platelet derived Beta2 microglobulin (β2M) is an immune
molecule that mediates a pro-inflammatory monocyte phenotype. Using our novel platelet specific β2M-/- mice
we have now found that platelets are a major source of plasma β2M, and that platelet derived β2M has direct
pro-inflammatory effects. This leads us to propose a novel mechanistic link between platelets, plasma β2M,
and immune cell responses, particularly platelet driven monocyte pro-inflammatory responses.
Hypothesis: β2M is a novel platelet derived mediator of a pro-inflammatory monocyte phenotype.
Specific Aim # 1. To demonstrate mechanisms of platelet mediated monocyte inflammatory phenotype
in vitro. We will use in vitro cell based studies to show how platelet derived β2M induces monocyte pro-
inflammatory responses.
Specific Aim # 2. To demonstrate how platelet-derived β2M mediates monocyte responses and
outcomes in an ischemic myocardial injury model. We will use our established myocardial infarction model
to demonstrate the pathophysiologic mechanism of β2M mediated ischemic tissue injury.
 This proposal will demonstrate novel mechanisms for platelet mediated monocyte activation that have
direct impacts on major causes of morbidity and mortality worldwide. Results of our studies will influence the
work of many other groups and research projects. This proposal consists of an ambitious set of studies that our
research team is uniquely situated to pursue.

## Key facts

- **NIH application ID:** 10166903
- **Project number:** 5R01HL141106-04
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** CRAIG N MORRELL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $464,364
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10166903

## Citation

> US National Institutes of Health, RePORTER application 10166903, Novel mechanisms of platelet modified monocyte phenotype (5R01HL141106-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10166903. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*