Innate Immune Cell Trafficking and Function During Sterile Inflammation of the Liver  Braedon McDonald, Paul Kubes  Gastroenterology  Volume 151, Issue 6, Pages 1087-1095 (December 2016) DOI: 10.1053/j.gastro.2016.09.048 Copyright © 2016 AGA Institute Terms and Conditions

Figure 1 Mechanisms of cell death. Schematic summary of cell death by apoptosis, necrosis, necroptosis, and pyroptosis. Noninflammatory cell death by apoptosis results in the retention of cellular contents within apoptotic bodies, as well as the release of keep-out signals to inhibit neutrophil recruitment. In contrast, inflammatory cell death occurs via passive (necrosis) and active mechanisms (necroptosis, pyroptosis) and results in the release of DAMPs and stimulation of sterile inflammation. Gastroenterology 2016 151, 1087-1095DOI: (10.1053/j.gastro.2016.09.048) Copyright © 2016 AGA Institute Terms and Conditions

Figure 2 Progression of the sterile inflammatory response and tissue repair. The timeline of the innate immune response to tissue injury is displayed, with corresponding phases of wound repair. In response to necrotic cell death in the liver (passive and active/programmed necrosis), the first immune cells to response are platelets, neutrophils, and GATA6+ peritoneal macrophages. Subsequently, inflammatory (CCR2hi) monocytes arrive at sites of injury, followed soon after by the appearance of noninflammatory/pro-resolution CX3CR1hi monocytes, either via de novo recruitment or in situ reprogramming of the monocyte phenotype. Together, these innate immune cells coordinate initiation of tissue repair through the clearance of debris and stimulation of extracellular matrix (ECM) formation and revascularization to enable parenchymal cell repopulation. Gastroenterology 2016 151, 1087-1095DOI: (10.1053/j.gastro.2016.09.048) Copyright © 2016 AGA Institute Terms and Conditions

Figure 3 Emergency repopulation of macrophages at sites of sterile inflammation in the liver. (Left) Kupffer cells reside within the vasculature, are nonmotile, and do not migrate to sites of damage. Blood-borne monocytes are recruited to foci of sterile inflammation, where they subsequently differentiate into macrophages at the site of injury. (Right) A unique population of peritoneal cavity macrophages (GATA6+) are attracted to sites of injury in the liver by adenosine triphosphate (ATP) danger signals released from dead hepatocytes. These cavity macrophages migrate across the liver capsule (not via blood vessels) into the parenchyma, where they accumulate at foci of injury and contribute to wound healing. Gastroenterology 2016 151, 1087-1095DOI: (10.1053/j.gastro.2016.09.048) Copyright © 2016 AGA Institute Terms and Conditions