mac1

Mac-1, also known as macrophage-1 antigen, is a cell-surface receptor that belongs to the integrin alpha chain family. In humans it is the αMβ2 integrin, formed by the αM chain (CD11b, encoded by ITGAM) and the β2 chain (CD18, encoded by ITGB2). Mac-1 is prominently expressed on myeloid lineage cells, including neutrophils, monocytes, macrophages, some dendritic cells, and certain natural killer cells. As a heterodimer, Mac-1 mediates both adhesion and recognition functions critical to innate immunity.

Mac-1 mediates firm adhesion of leukocytes to endothelial cells by binding to intercellular adhesion molecule 1 (ICAM-1) and ICAM-2, enabling transmigration into tissues. It also recognizes opsonized pathogens via binding to complement fragment iC3b, supporting phagocytosis and clearance of microbes and immune complexes. Through these activities, Mac-1 contributes to inflammation, wound healing, and host defense, as well as clearance of apoptotic cells and debris.

Activation of Mac-1 is regulated by inside-out signaling, which increases its affinity for ligands in response to chemokines and other stimuli. Upon engagement, outside-in signaling triggers cytoskeletal rearrangements, respiratory burst, and phagocytic cup formation. Mac-1 can bind multiple ligands including bacteria, fungal components, and extracellular matrix proteins, reflecting its role as a versatile pattern-recognition and adhesion receptor.

Clinical interest centers on modulating Mac-1 activity to control leukocyte recruitment in inflammatory and autoimmune diseases. Hypo- or hyperactivity of Mac-1 has been linked to impaired host defense or excessive tissue damage. Therapeutic approaches include antibodies and small molecules aimed at inhibiting Mac-1–ICAM interactions or altering its activation state, with ongoing research in sepsis, rheumatoid arthritis, and other inflammatory conditions.