Mac1ICAM

Mac1ICAM refers to the functional adhesion interface formed between the leukocyte integrin Mac-1 and ICAM family ligands, most notably ICAM-1, during immune cell trafficking. It is not a separate protein unit, but the binding interaction that mediates stable adhesion of leukocytes to endothelial cells and subsequent transmigration during inflammatory responses.

Mac-1 is the integrin αMβ2, comprised of the CD11b (αM) and CD18 (β2) subunits. The ligand-binding site resides mainly in the αM I-domain and engages ICAM-1 through a calcium- and magnesium-dependent mechanism. Binding affinity is typically in the low micromolar range and is regulated by conformational changes in Mac-1 that convert the molecule from a low- to a high-affinity state. Inside-out signaling—driven by chemokines, complement fragments, and integrin-activating pathways—induces these conformational changes, enabling the Mac-1ICAM interaction under physiological shear conditions.

Regulation of Mac-1ICAM binding involves cytoplasmic adaptor proteins such as talin and kindlin-3, which promote activation of Mac-1, and external signals that modulate leukocyte adhesion strength. The interaction can be modulated by the presence of other ligands for Mac-1, as well as by post-translational modifications on ICAM-1 and the integrin subunits.

Biological roles include mediating neutrophil and monocyte firm adhesion to activated endothelium, supporting diapedesis, and contributing to phagocytosis and antigen presentation. Clinically, dysregulation of Mac-1ICAM interactions is implicated in inflammatory diseases, while therapeutic strategies have explored antagonists to block this axis to reduce tissue injury in conditions such as sepsis, rheumatoid arthritis, and other inflammatory disorders. Mac-1 and ICAM other family members also participate in related adhesion pathways, illustrating the broader context of the Mac-1ICAM axis in immune surveillance.