The platelet P2 receptors in inflammation
1Marco Cattaneo, MD, Divisione di Medicina Generale III, Azienda Ospedaliera San Paolo, Dipartimento di Scienze della Salute, Università degli Studi di Milano, Via di Rudinì, 8, 20142 Milano, Italy, Tel. +39/02 50 32 30-95, Fax -89.
Hamostaseologie
|January 13, 2015
Summary
Platelets and adenine nucleotides, via the P2Y12 receptor, promote inflammation in asthma. Targeting P2Y12 with antagonists like prasugrel may reduce bronchial hyper-reactivity in allergic asthma patients.
Area of Science:
- Immunology
- Pharmacology
- Respiratory Medicine
Background:
- Platelets play a role in inflammation beyond hemostasis.
- Adenine nucleotides act as signaling molecules via P2 receptors, influencing cellular functions.
- Emerging evidence highlights the pro-inflammatory roles of platelet P2 receptors.
Purpose of the Study:
- To investigate the role of platelet P2Y12 receptor in allergic asthma pathogenesis.
- To explore the therapeutic potential of P2Y12 antagonism in asthma.
Main Methods:
- Utilized experimental asthma models in mice.
- Analyzed P2Y12 variants in relation to lung function in an asthma cohort.
- Conducted a randomized, placebo-controlled trial of a P2Y12 antagonist (prasugrel) in allergic asthma patients.
Main Results:
- Platelet P2Y12 receptor significantly contributed to pro-inflammatory effects of cysteinyl leukotrienes in mouse asthma models.
- P2Y12 variants were associated with lung function in a family-based asthma cohort.
- Prasugrel showed a trend towards decreasing mannitol-induced bronchial hyper-reactivity in allergic asthma patients.
Conclusions:
- P2Y12 receptor is implicated in the inflammatory processes of allergic bronchial asthma.
- P2Y12 antagonism presents a potential therapeutic strategy for allergic asthma.
Related Concept Videos
01:20Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors
1.6K
Antiplatelet drugs emerge as frontline defenders against the insidious threat of thromboembolic diseases, where abnormal clots obstruct vital blood vessels. These drugs stand as bulwarks, inhibiting platelet aggregation and clot formation, thereby mitigating the risk of life-threatening conditions like myocardial infarction, coronary artery disease, and thrombotic strokes.
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
1.6K
01:22Formation of the Platelet Plug
11.1K
The platelet phase, the second stage of hemostasis, commences around 15-20 seconds after an injury. It follows and overlaps with the vascular phase, during which blood vessels constrict to minimize blood loss.
As the injured blood vessel contracts, endothelial cells undergo contraction, revealing collagen fibers in the basement membrane and underlying connective tissue. Furthermore, the plasma membrane of endothelial cells becomes adhesive, preparing the site for platelet adhesion. Platelets...
As the injured blood vessel contracts, endothelial cells undergo contraction, revealing collagen fibers in the basement membrane and underlying connective tissue. Furthermore, the plasma membrane of endothelial cells becomes adhesive, preparing the site for platelet adhesion. Platelets...
11.1K
01:25Acute Inflammation II: Local and Systemic Effects
6
Acute inflammation produces a coordinated set of local and systemic changes that limit injury, eliminate pathogens, and initiate repair. These responses arise within minutes of infection, trauma, or chemical insult and are driven by vascular alterations and leukocyte-derived mediators. When the stimulus resolves, the reaction typically abates within days.Local EffectsAt the site of injury, arteriolar vasodilation increases blood flow, resulting in redness and warmth. Simultaneously, increased...
6
01:18Structure and Function of Platelets
7.1K
The cell fragments known as platelets are disc-shaped, with an average diameter of about 3 μm and a thickness of roughly 1 μm. They play a crucial role in the body's vascular clotting system, which also involves plasma proteins, blood cells, and blood vessel tissues.
Platelets are continually replenished, circulating in the bloodstream for 9-12 days before being removed by phagocytes, primarily in the spleen. A microliter of circulating blood contains between 150,000 and 450,000...
Platelets are continually replenished, circulating in the bloodstream for 9-12 days before being removed by phagocytes, primarily in the spleen. A microliter of circulating blood contains between 150,000 and 450,000...
7.1K
01:38Inflammation
65.9K
Overview
65.9K
01:26Acute Inflammation I: Inflammatory Response
2
Acute inflammation is a rapid, short-lived physiological response to tissue injury or infection, designed to eliminate harmful agents and initiate repair. This tightly regulated process typically lasts from minutes to several days and is triggered by factors such as microbial invasion, physical trauma, or chemical injury.Recognition and Mediator ReleaseThe inflammatory response begins when resident immune cells—such as mast cells, macrophages, and dendritic cells—detect...
2