IMP and AMP deaminase in reperfusion injury down-regulates neutrophil recruitment

Qiu, Fei-Hua; Wada, Koichiro; Stahl, Gregory L.; Serhan, Charles N.

doi:10.1073/pnas.97.8.4267

Cited by 44 publications

(63 citation statements)

References 34 publications

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“…These actions were coupled with a reduction in systemic inflammatory markers, findings that are concurrent with protective actions afforded by AnxA1 during ischemia/reperfusion injury in a number of murine models (10,27). Repair of damaged tissue and prevention of further damage by mediators released from necrotic cells is also critical to ensure organ protection after ischemia/reperfusion injury (41). The AnxA1 pathway also exerts direct protective actions on cardiomyocytes preserving resting contractile function after metabolic inhibition (42) or exposure to proinflammatory mediators (43).…”

Section: Discussionmentioning

confidence: 99%

Proresolving and Tissue-Protective Actions of Annexin A1–Based Cleavage-Resistant Peptides Are Mediated by Formyl Peptide Receptor 2/Lipoxin A4 Receptor

Dalli

Consalvo²,

Ray³

et al. 2013

The Journal of Immunology

109

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Endogenous mechanisms regulating the host response during inflammation resolution are critical in ensuring disposal of noxious stimuli and return to homeostasis. In this article, we engineered novel Annexin A1 (AnxA1)–based peptides, AnxA12–50, that displayed specific binding to the AnxA1 receptor (formyl peptide receptor 2/Lipoxin A4 receptor [FPR2/ALX]; IC50 ∼4 nM). Intravenous administration of AnxA12–50 markedly reduced (>60%) leukocyte adhesion to postcapillary venules in wild type and Fpr1−/−, but not Fpr2/Alx−/−, mice. Generation of a metabolically stable form of this peptide (CR-AnxA12–50), engineered by substituting a cleavage site shared by human proteinase 3 and neutrophil elastase, yielded an agonist that was resistant to neutrophil-mediated cleavage and displayed enhanced proresolving actions: accelerated resolution of self-limited inflammation and enhanced macrophage efferocytosis after sterile injury, when compared with AnxA12–50. These actions were retained with human primary leukocytes where CR-AnxA12–50 decreased neutrophil–endothelial interactions (∼25–45%), and stimulated neutrophil apoptosis and macrophage efferocytosis (∼45%). In murine cardiac ischemia/reperfusion injury, CR-AnxA12–50 elicited tissue-protective actions reducing infarct size (∼60%) and incidence of 24-h death. These results identify AnxA12–50 and CR-AnxA12–50 as FPR2/ALX agonists that harness the proresolving actions of AnxA1, and thus may represent therapeutic tools for treatment of inflammatory conditions.

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Section: Discussionmentioning

confidence: 99%

Proresolving and Tissue-Protective Actions of Annexin A1–Based Cleavage-Resistant Peptides Are Mediated by Formyl Peptide Receptor 2/Lipoxin A4 Receptor

Dalli

Consalvo²,

Ray³

et al. 2013

The Journal of Immunology

109

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“…IMP has also been shown to be anti-inflammatory (Qiu et al 2000, Li et al 2007, an effect that may also be mediated through the pathways activated by inosine. Indeed, inhibition of IMP dehydrogenase (IMPDH) by mycophenolate mofetil (MMF) has proved effective in transplant rejection and also in a variety of autoimmune diseases (Allison & Eugui 2000) including type I diabetes , StosicGrujicic et al 2002.…”

Section: Discussionmentioning

confidence: 99%

The novel inosine analogue, INO-2002, protects against diabetes development in multiple low-dose streptozotocin and non-obese diabetic mouse models of type I diabetes

Mabley

Pacher

Murthy

et al. 2008

Journal of Endocrinology

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Endogenous purines including inosine have been shown to exert immunomodulatory and anti-inflammatory effects in a variety of disease models. The dosage of inosine required for protection is very high because of the rapid metabolism of inosine in vivo. The aim of this study was to determine whether a metabolic-resistant purine analogue, INO-2002, exerts antiinflammatory effects in two animal models of type I diabetes.

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“…To determine whether our composite vector is responsive to hypoxia in vivo in multiple tissues, we injected 6-to 8-week-old Sprague-Dawley rats with 4 ϫ 10 11 viral infectious particles of either AAV-4EpoHRE-mSV40-LacZ or AAV-4EpoHRE-mSV40-HO-1 via direct injection into the skeletal muscle and heart and via the portal vein to the liver. Five weeks after therapeutic gene delivery into the tibialis anterior muscle of the left limb, I͞R was induced by the tourniquet method (19). In the animals injected with the vector but without I͞R injury, we could not detect any transgene expression by semiquantitative RT-PCR up to 38 cycles, indicating little or negligible gene expression.…”

Section: Ischemic Induction Of Hho-1 Prevents I͞r-mediated Injury In mentioning

confidence: 99%

“…Animals were killed at 24 h after reperfusion. For hind limb I͞R, a tourniquet method was used as described (19).…”

Section: Methodsmentioning

confidence: 99%

Hypoxia-regulated therapeutic gene as a preemptive treatment strategy against ischemia/reperfusion tissue injury

Pachori

Melo

Hart

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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Ischemia and reperfusion represent major mechanisms of tissue injury and organ failure. The timing of administration and the duration of action limit current treatment approaches using pharmacological agents. In this study, we have successfully developed a preemptive strategy for tissue protection using an adenoassociated vector system containing erythropoietin hypoxia response elements for ischemia-regulated expression of the therapeutic gene human heme-oxygenase-1 (hHO-1). We demonstrate that a single administration of this vector several weeks in advance of ischemia͞reperfusion injury to multiple tissues such as heart, liver, and skeletal muscle yields rapid and timely induction of hHO-1 during ischemia that resulted in dramatic reduction in tissue damage. In addition, overexpression of therapeutic transgene prevented long-term pathological tissue remodeling and normalized tissue function. Application of this regulatable system using an endogenous physiological stimulus for expression of a therapeutic gene may be a feasible strategy for protecting tissues at risk of ischemia͞reperfusion injury.

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IMP and AMP deaminase in reperfusion injury down-regulates neutrophil recruitment

Cited by 44 publications

References 34 publications

Proresolving and Tissue-Protective Actions of Annexin A1–Based Cleavage-Resistant Peptides Are Mediated by Formyl Peptide Receptor 2/Lipoxin A4 Receptor

Proresolving and Tissue-Protective Actions of Annexin A1–Based Cleavage-Resistant Peptides Are Mediated by Formyl Peptide Receptor 2/Lipoxin A4 Receptor

The novel inosine analogue, INO-2002, protects against diabetes development in multiple low-dose streptozotocin and non-obese diabetic mouse models of type I diabetes

Hypoxia-regulated therapeutic gene as a preemptive treatment strategy against ischemia/reperfusion tissue injury

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