Interactions between activated α4β1 and α5β1 integrins expressed on leukocytes and cellular fibronectin, newly synthesized by endothelial cells after injury, favor the induction of MMP-9 expression by leukocytes. Cytokines and other pro-inflammatory factors, such as iNOS-derived NO produced during the acute phase of IRI, can also mediate MMP-9 activation. MMP-9 assisted focal matrix degradation facilitates leukocyte transmigration into the liver. In addition, MMP-9+ leukocytes infiltrating livers after IRI can cause parenchyma cell detachment from ECM and, consequently promote apoptosis/anoikis of these cells leading to tissue injury.