Related Experiment Video
Updated: Apr 5, 2026
08:15
In Situ Exploration of Murine Megakaryopoiesis using Transmission Electron Microscopy
Published on: September 8, 2021
3.4K
Intramedullary megakaryocytes internalize released platelet factor 4 and store it in alpha granules
M P Lambert1,2, R Meng3, L Xiao2
1Department of Pediatrics Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Journal of Thrombosis and Haemostasis : JTH
|August 11, 2015
Summary
Platelet factor 4 (PF4) has a complex life cycle within bone marrow, influencing blood cell production. This study defines its source and intramedullary behavior, revealing implications for megakaryopoiesis and stem cell replication.
Area of Science:
- Hematology
- Cell Biology
- Molecular Biology
Background:
- Megakaryocytes (MKs) store and release platelet factor 4 (PF4) from alpha granules.
- PF4 negatively regulates megakaryopoiesis and hematopoietic stem cell (HSC) replication in vivo.
- A regulated source of free intramedullary PF4 is suggested by these observations.
Purpose of the Study:
- To define the source of free intramedullary PF4.
- To elucidate the intramedullary life cycle of PF4.
Main Methods:
- In vitro studies using murine and human bone marrow-derived cells during megakaryopoiesis.
- Confocal microscopy and enzyme-linked immunosorbent assay (ELISA) were employed.
- In vivo immunohistochemistry examined free PF4 in murine bone marrow before and after radiation injury, and in settings of megakaryocytopenia and thrombocytopenia.
Main Results:
- Murine megakaryocytes internalize exogenous PF4, which colocalizes with endogenous PF4 in alpha granules and is releasable upon thrombin stimulation.
- Free PF4 is detected in bone marrow, increasing with radiation injury and decreasing with megakaryocytopenia.
- PF4 internalization is partially dependent on low-density lipoprotein receptor-related protein 1 (LRP1), implicating it in PF4's paracrine effects.
Conclusions:
- PF4 exhibits a complex intramedullary life cycle.
- This cycle has significant implications for megakaryopoiesis and HSC replication.
- These effects are distinct from other alpha granule proteins studied.
Related Concept Videos
01:18Structure and Function of Platelets
5.4K
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...
5.4K
01:22Formation of the Platelet Plug
10.8K
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...
10.8K
01:15Differentiation of Common Myeloid Progenitor Cells
4.2K
Common myeloid progenitors (CMPs) are oligopotent cells that can differentiate into granulocytes and macrophages. Granulocytes and macrophages are essential for protecting the body against bacterial, viral, or fungal infections. They migrate from the bone marrow into the circulating blood to reach specific tissue sites where they differentiate and help in immune surveillance. However, they survive only for a few days and must be continuously made available to the organism to maintain a robust...
4.2K
01:17Intracellular Signaling Affects Focal Adhesions
3.8K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
3.8K
01:16Clot Retraction and Fibrinolysis
10.3K
After a fibrin clot is formed, the next step is clot retraction, a vital process facilitated by platelet contractile proteins, such as actin and myosin. These proteins pull the fibrin strands closer together and condense the clot. This action reduces the size of the clot, creating a smaller, denser structure that effectively seals off the damaged vessel. Clot retraction consolidates the clot and helps with wound healing by bringing the edges of the damaged blood vessel closer together.
10.3K
01:20Extrinsic and Intrinsic Pathways of Hemostasis
15.5K
Blood clotting or coagulation involves extrinsic and intrinsic pathways, which ultimately merge into the common pathway, forming a fibrin clot.
The Extrinsic Pathway
The extrinsic pathway of coagulation is typically initiated by tissue damage that exposes blood to tissue factor (TF), a protein released by the damaged tissue cells outside the blood vessels—this interaction with TF triggers biochemical reactions involving specific clotting factors. The key player here is Factor VII, which...
The Extrinsic Pathway
The extrinsic pathway of coagulation is typically initiated by tissue damage that exposes blood to tissue factor (TF), a protein released by the damaged tissue cells outside the blood vessels—this interaction with TF triggers biochemical reactions involving specific clotting factors. The key player here is Factor VII, which...
15.5K