Regulation of monocyte migration by amphoterin (HMGB1)

Area of Science:

• Immunology
• Cell Biology
• Biochemistry

Background:

• Amphoterin (High Mobility Group Box 1 protein, HMGB1) is a heparin-binding protein implicated in cell migration via the receptor for advanced glycation end products (RAGE).
• Elevated serum amphoterin levels are observed during septic shock.
• The role of amphoterin and RAGE in monocyte behavior, particularly transendothelial migration, requires further investigation.

Purpose of the Study:

• To investigate the expression of amphoterin on monocytes.
• To elucidate the function of amphoterin and RAGE in monocyte adhesion and transendothelial migration.

Main Methods:

• Immunohistochemical staining of arterial thrombi.
• Monocyte adhesion assays using peripheral blood leukocytes.
• Functional assays involving blocking antibodies and soluble RAGE.
• Assessment of amphoterin secretion from activated macrophages, including inhibition studies targeting ATP-binding cassette transporter-1.

Main Results:

• Unactivated monocytes do not express surface amphoterin, but adherent monocytes do.
• Amphoterin is present in mononuclear cells and extracellular matrix within arterial thrombi.
• Amphoterin mediates monocyte adhesion and cell spreading in a RAGE-dependent manner.
• Macrophage secretion of amphoterin is regulated by the ATP-binding cassette transporter-1.
• Inhibition of amphoterin or RAGE significantly reduces monocyte transendothelial migration.

Conclusions:

• Amphoterin is expressed on the surface of adherent monocytes and plays a role in their adhesion and migration.
• The interaction between amphoterin and RAGE is crucial for monocyte invasion across the endothelium.
• Amphoterin may function as an autocrine/paracrine regulator of monocyte endothelial transmigration.