biostudies-literaturePoole LGNational Institute of Environmental Health SciencesNational Institute of Diabetes and Digestive and Kidney DiseasesNIDDK NIH HHSU.S. Department of AgricultureNIEHS NIH HHS1182-1192https://www.ebi.ac.uk/biostudies/studies/S-EPMC9035112biostudies-literatureUnknown20(5)<h4>Background</h4>The blood coagulation factor fibrin(ogen) can modulate inflammation by altering leukocyte activity. Analyses of fibrin(ogen)-mediated proinflammatory activity have largely focused on leukocyte integrin binding activity revealed by conversion of fibrinogen to a stabilized fibrin polymer by blood coagulation enzymes. In addition to coagulation enzymes, fibrinogen is a substrate for tissue transglutaminase-2 (TG2), a widely expressed enzyme that produces unique fibrinogen Aα-γ chain cross-linked products.<h4>Objectives</h4>We tested the hypothesis that TG2 dependent cross-linking alters the proinflammatory activity of surface-adhered fibrinogen.<h4>Methods</h4>Mouse bone marrow-derived macrophages (BMDMs) were cultured on tissue culture plates coated with fibrinogen or TG2-Journal of thrombosis and haemostasis : JTHCross-linking by tissue transglutaminase-2 alters fibrinogen-directed macrophage proinflammatory activity.PMC9035112F32DK121423K99 DK129710K99DK129710R01 DK120289F32 DK121423R01DK120289R01DK112778R01ES017537R01 ES017537Flick MJKopec AKLuyendyk JPPoole LGfalseCross-linking by tissue transglutaminase-2 alters fibrinogen-directed macrophage proinflammatory activity.<h4>Background</h4>The blood coagulation factor fibrin(ogen) can modulate inflammation by altering leukocyte activity. Analyses of fibrin(ogen)-mediated proinflammatory activity have largely focused on leukocyte integrin binding activity revealed by conversion of fibrinogen to a stabilized fibrin polymer by blood coagulation enzymes. In addition to coagulation enzymes, fibrinogen is a substrate for tissue transglutaminase-2 (TG2), a widely expressed enzyme that produces unique fibrinogen Aα-γ chain cross-linked products.<h4>Objectives</h4>We tested the hypothesis that TG2 dependent cross-linking alters the proinflammatory activity of surface-adhered fibrinogen.<h4>Methods</h4>Mouse bone marrow-derived macrophages (BMDMs) were cultured on tissue culture plates coated with fibrinogen or TG2-2022-01-01T00:00:00Z2022 May2025-04-27T04:21:30.653Z2025-02-19T04:20:56.09ZS-EPMC90351123515841310.1111/jth.15670