Does inhibition of plasmin protect against colitis in mice by suppressing matrix metalloproteinase 9-mediated cytokine release from myeloid cells?
In mice, plasmin induces a feedback mechanism in which activation of the fibrinolytic system promotes the development of colitis via activation of MMP9 or proteolytic enzymes. The proteolytic environment stimulates the influx of myeloid cells into the colonic epithelium and the production of tumor necrosis factor and C-X-C motif chemokine ligand 5. In turn, myeloid CD11b+ cells release the urokinase plasminogen activator, which accelerates plasmin production. Disruption of the plasmin-induced chronic inflammatory circuit therefore might be a strategy for colitis treatment.
Enhancing NO bioavailability via exogen application of NOSs and L-arginine significantly attenuated ischemia-reperfusion-induced microcirculatory alterations in the microvasculature of skeletal muscle. Significant hemodynamic adverse effects were not present, thus demonstrating this approach might be useful for therapeutic intervention. This "pharmacologic preconditioning" could be an easy and effective interventional strategy to uphold conversation of L-arginine to NO under ischemic conditions.