ITGAM
Description
The ITGAM (integrin subunit alpha M) is a protein-coding gene located on chromosome 16.
ITGAM is a protein subunit that forms the αMβ2 integrin molecule, also known as Mac-1 or CR3. This integrin is expressed on various leukocytes involved in innate immunity, including monocytes, granulocytes, macrophages, and natural killer cells. αMβ2 plays a key role in inflammation by regulating leukocyte adhesion and migration. ITGAM is also involved in immune processes such as phagocytosis, cell-mediated cytotoxicity, chemotaxis, and cellular activation. It is essential for binding the inactivated complement component 3b (iC3b). ITGAM, as part of the αMβ2 complex, contributes to cell adhesion and spreading, but cannot mediate cell migration without the presence of the β2 (CD18) subunit. Genetic studies have linked single nucleotide polymorphisms in ITGAM to an increased risk of systemic lupus erythematosus. In histopathology, antibodies against CD11B are used to identify macrophages and microglia. CD11B is essential for leukocyte migration, adhesion, and transmigration across blood vessels due to its ability to bind to components of the extracellular matrix and intracellular adhesion molecules (ICAMs) on the endothelial surface.
ITGAM, along with its beta subunit ITGB2, plays a crucial role in the adhesion and migration of various immune cells, including monocytes, macrophages, and granulocytes. This heterodimer acts as a receptor for the iC3b fragment of complement component 3, likely recognizing the R-G-D peptide within C3b. Furthermore, ITGAM/ITGB2 functions as a receptor for fibrinogen, factor X, and ICAM1, interacting with specific peptides within the fibrinogen gamma chain. ITGAM/ITGB2 regulates neutrophil migration, and in conjunction with ITGB2/CD18, is essential for CD177-PRTN3-mediated activation of TNF-primed neutrophils. ITGAM is implicated in regulating phagocytosis-induced apoptosis in extravasated neutrophils and may contribute to mast cell development. In microglia, ITGAM, in combination with TYROBP/DAP12, controls the production of superoxide ions, which promote neuronal apoptosis during brain development.
ITGAM is also known as CD11B, CR3A, MAC-1, MAC1A, MO1A, SLEB6.
