Integrin modulating factor-1: A lipid that alters the function of leukocyte integrins

The avidity of integrin CR3 (also known as α M β 2 , Mac-1, Mo-1, and CD11bCD18) may be reversibly altered without changes in the number of cell surface receptors. Here we describe a molecule termed integrin modulating factor (IMF-1), which controls CR3 avidity. Addition of IMF-1 to polymorphonuclear leukocytes (PMNs) or to purified CR3 causes enhanced binding of ligand. IMF-1 is not present in resting PMNs, but stimulation of cells results in a transient rise in IMF-1 content that parallels a transient rise in CR3 activity. We suggest that PMNs control adhesivity by controlling synthesis of IMF-1, which then acts as an allosteric activator of leukocyte integrins. IMF-1 is an acidic, amphiphilic molecule of M r 340 ± 16 that does not contain ester, phosphate, amide, sialic acid, or glycosidic or vicinal hydroxyl functionalities, but does contain a carbon-carbon double bond. These results suggest that IMF-1 is an unsaturated fatty acid or an isoprenoid acid.