Tanya Mayadas of the Department of Pathology and colleagues have uncovered how alterations in “catch bonds” may contribute to lupus susceptibility. Their work appears in the March 12 issue of Cell Reports.
A catch bond is a type of adhesive bond that is strengthened by mechanical force, and thus allows white blood cells to stably roll on, and adhere to the vessel wall, and to perform other important functions during an immune response. Genetic studies and mouse models of lupus, an autoimmune disease, have suggested that defects in Mac-1 may contribute to susceptibility for the disease. Mac-1 is a cell surface receptor on white blood cells that undergoes conformational changes (“activation”) needed to increase its ability to bind its ligands (signal-triggering molecules), which in turn affects white blood cell functions.
Mayadas et al.’s studies show that a Mac-1 variant that significantly associates with lupus susceptibility in humans has reduced ability to form catch bonds, which could be reversed by targeted mutations and activating antibodies that induce the full activation of Mac-1.
“Our data…suggest that elimination of catch bonds may have pathological consequences,” the authors write.