Anti-P-selectin antibody protects against hepatic ichemia–reperfusion injury

Singh, Inderjeet; Zibari, Gazi B.; Zizzi, H; Granger, D. Neil; Cruz, L.; Gonsales, E. B.; McDonald, John C.; Brown, Mark F.

doi:10.1016/s0041-1345(98)00640-x

Cited by 17 publications

(12 citation statements)

References 5 publications

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“…Leukocyte rolling in mice subjected to I/R injury followed a bimodal peak as demonstrated by previous research in our lab [8]. This bimodal peak was also seen in mice undergoing IPC but was significantly attenuated when compared to nonpreconditioned mice.…”

Section: Rollingsupporting

confidence: 81%

See 1 more Smart Citation

The Role of Ischemic Preconditioning in the Recruitment of Rolling and Adherent Leukocytes in Hepatic Venules after Ischemia/Reperfusion

Sawaya

Brown

Minardi

et al. 1999

Journal of Surgical Research

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Section: Rollingsupporting

confidence: 81%

“…P-selectin is a transmembrane glycoprotein associated with alpha granules in endothelial cells known as Weibel-Palade bodies [6,7]. A bimodal peak of P-selectin activity has been demonstrated following 30 min of hepatic ischemia [8]. The first peak at 30 min reperfusion is felt to be from release of preformed P-selectin.…”

Section: Introductionmentioning

confidence: 99%

The Role of Ischemic Preconditioning in the Recruitment of Rolling and Adherent Leukocytes in Hepatic Venules after Ischemia/Reperfusion

Sawaya

Brown

Minardi

et al. 1999

Journal of Surgical Research

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“…Because inhibition of apoptosis, IL-6, or P-selectin has been demonstrated to protect against I/R-induced organ failure in the kidney, 15,[22][23][24] heart, 35,36 brain, 37,38 intestine, 39 and liver, 40 GC-G may also be involved in I/R-induced abnormalities in other organs, such as acute myocardial infarction in the heart or stroke in the brain, which warrants further investigation. Although the exact mechanism by which GC-G is regulated under renal I/R remains undefined, a simple regulatory mechanism could be that renal I/R induces the release of endogenous ligand(s) and modulates GC-G activity to transmit the injury signal leading to apoptosis and inflammation.…”

Section: Discussionmentioning

confidence: 99%

Disruption of Guanylyl Cyclase-G Protects against Acute Renal Injury

Lin

Cheng²,

Hou

et al. 2008

Journal of the American Society of Nephrology

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The membrane forms of guanylyl cyclase (GC) serve as cell-surface receptors that synthesize the second messenger cGMP, which mediates diverse cellular processes. Rat kidney contains mRNA for the GC-G isoform, but the role of this receptor in health and disease has not been characterized. It was found that mouse kidney also contains GC-G mRNA, and immunohistochemistry identified GC-G protein in the epithelial cells of the proximal tubule and collecting ducts. Six hours after ischemia-reperfusion (I/R) injury, GC-G mRNA and protein expression increased three-fold and remained upregulated at 24 h. For determination of whether GC-G mediates I/R injury, a mutant mouse with a targeted disruption of the GC-G gene (Gucy2g) was created. At baseline, no histologic abnormalities were observed in GC-G Ϫ/Ϫ mice. After I/R injury, elevations in serum creatinine and urea were attenuated in GC-G Ϫ/Ϫ mice compared with wild-type controls, and this correlated with less tubular disruption, less tubular cell apoptosis, and less caspase-3 activation. Measures of inflammation (number of infiltrating neutrophils, myeloperoxidase activity, and induction of IL-6 and P-selectin) and activation of NF-B were lower in GC-G Ϫ/Ϫ mice compared with wild-type mice. Direct transfer of a GC-G expression plasmid to the kidneys of GC-G Ϫ/Ϫ mice resulted in a dramatically higher mortality after renal I/R injury, further supporting a role for GC-G in mediating injury. In summary, GC-G may act as an early signaling molecule that promotes apoptotic and inflammatory responses in I/R-induced acute renal injury.

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“…The blockade of P-selectin and PSGL-1 protects the liver from IRI (13)(14)(15)(16)(17). We have also shown that blockade of the interaction between P-selectin and PSGL-1 with a recombinant soluble form of P-selectin glycoprotein ligand-1 (rPSGL-Ig) decreased portal resistance, increased bile production, and reduced polymorphonuclear leukocyte (PMN) infiltration in steatotic rat liver models of ex vivo cold ischemia followed by reperfusion.…”

mentioning

confidence: 99%

Molecular Characterization of Rat Leukocyte P-Selectin Glycoprotein Ligand-1 and Effect of Its Blockade: Protection from Ischemia-Reperfusion Injury in Liver Transplantation

Tsuchihashi

Fondevila

Shaw³

et al. 2006

The Journal of Immunology

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P-selectin glycoprotein ligand-1 (PSGL-1) mediates the initial tethering of leukocytes to activated platelets and endothelium. We report molecular cloning and characterization of the rat PSGL-1 gene. A neutralizing Ab was generated, and its binding epitope was mapped to the N-terminal binding region of rat PSGL-1. We examined the effects of early PSGL-1 blockade in rat liver models of cold ischemia, followed by ex vivo reperfusion or transplantation (orthotopic liver transplantation (OLT)) using an anti-PSGL-1 Ab with diminished Fc-mediated effector function. In the ex vivo hepatic cold ischemia and reperfusion model, pretreatment with anti-PSGL-1 Ab improved portal venous flow, increased bile production, and decreased hepatocellular damage. Rat pretreatment with anti-PSGL-1 Ab prevented hepatic insult in a model of cold ischemia, followed by OLT, as assessed by 1) decreased hepatocellular damage (serum glutamic oxaloacetic transaminase/glutamic-pyruvic transaminase levels), and ameliorated histological features of ischemia/reperfusion injury, consistent with extended OLT survival; 2) reduced intrahepatic leukocyte infiltration, as evidenced by decreased expression of P-selectin, ED-1, CD3, and OX-62 cells; 3) inhibited expression of proinflammatory cytokine genes (TNF-α, IL-1β, IL-6, IFN-γ, and IL-2); and 4) prevented hepatic apoptosis accompanied by up-regulation of antiapoptotic Bcl-2/Bcl-xL protective genes. Thus, targeting PSGL-1 with a blocking Ab that has diminished Fc-mediated effector function is a simple and effective strategy that provides the rationale for novel therapeutic approaches to maximize the organ donor pool through the safer use of liver transplants despite prolonged periods of cold ischemia.

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Anti-P-selectin antibody protects against hepatic ichemia–reperfusion injury

Cited by 17 publications

References 5 publications

The Role of Ischemic Preconditioning in the Recruitment of Rolling and Adherent Leukocytes in Hepatic Venules after Ischemia/Reperfusion

The Role of Ischemic Preconditioning in the Recruitment of Rolling and Adherent Leukocytes in Hepatic Venules after Ischemia/Reperfusion

Disruption of Guanylyl Cyclase-G Protects against Acute Renal Injury

Molecular Characterization of Rat Leukocyte P-Selectin Glycoprotein Ligand-1 and Effect of Its Blockade: Protection from Ischemia-Reperfusion Injury in Liver Transplantation

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