Prevention of primary graft dysfunction in lung transplantation by N-acetylcysteine after prolonged cold ischemia

İnci, İlhan; Erne, Barbara; Arni, Stephan; Jungraithmayr, Wolfgang; Inci, Demet; Hillinger, Sven; Vogt, Peter R.; Leskosek, B.; Weder, Walter

doi:10.1016/j.healun.2010.06.017

Cited by 32 publications

(25 citation statements)

References 37 publications

(35 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[13][14][15] Volatile anesthetics were demonstrated to attenuate reperfusion injury in vivo 16 -18 and to decrease the up-regulation of inflammatory adherence molecules of stimulated neutrophils in vitro. 19 -21 Therefore, we hypothesized that volatile anesthetics not only attenuate up-regulation of cell surface molecules, but also reduce the release of MMP-9, stored in neutrophil granules.…”

mentioning

confidence: 99%

Volatile Anesthetics Reduce Invasion of Colorectal Cancer Cells through Down-regulation of Matrix Metalloproteinase-9

Müller‐Edenborn

Roth-Z'Graggen²,

Bartnicka³

et al. 2012

Anesthesiology

View full text Add to dashboard Cite

Background Invasion of extracellular matrix is a hallmark of malignant tumors. Clamping maneuvers during cancer surgery reduce blood loss, but trigger reperfusion injury (RI). RI increases cancer recurrence in the reperfused organ through up-regulation of matrix metalloproteinase-9 (MMP-9). Interleukin-8 is an important cytokine in RI promoting accumulation of neutrophils, a major source of MMP-9. Volatile anesthetics were demonstrated to reduce RI. We hypothesized that these anesthetics might attenuate MMP-9 up-regulation and consequently tumor cell invasion in RI. Methods Isolated human neutrophils (n = 6) were preconditioned with sevoflurane or desflurane, followed by stimulation with interleukin-8, phorbol myristate acetate, or chemokine CXC-ligand 1 (CXCL1) to differentiate intracellular pathways. MMP-9 release and activity were quantified by enzyme-linked immunosorbent assay and zymography, respectively. CXC-receptor-2 (CXCR2) expression and phosphorylation of extracellular signal-regulated kinases 1/2 were assessed by flow cytometry. The impact of MMP-9 on the invasion of neutrophils and MC-38 colon cancer cells was assessed using Matrigel-coated filters (n = 6). Results Preconditioning reduced interleukin-8-induced MMP-9-release by 41% (±13, 5%, sevoflurane) and 40% (±13%, desflurane). This was also evident following stimulation of CXCR2 with CXCL1. No impact on phosphorylation of extracellular signal-regulated kinases 1/2 and MMP-9 release was observed with receptor-independent stimulation of protein kinase C with phorbol myristate acetate. Preconditioning reduced transmigration of neutrophils and MC-38 tumor cells to baseline levels. Discussion Volatile anesthetics impair neutrophil MMP-9 release and interfere with pathways downstream of CXCR2, but upstream of protein kinase C. Through down-regulation of MMP-9, volatile anesthetics decrease Matrigel breakdown and reduce subsequent migration of cancer cells in vitro.

show abstract

mentioning

confidence: 99%

Volatile Anesthetics Reduce Invasion of Colorectal Cancer Cells through Down-regulation of Matrix Metalloproteinase-9

Müller‐Edenborn

Roth-Z'Graggen²,

Bartnicka³

et al. 2012

Anesthesiology

View full text Add to dashboard Cite

show abstract

“…Sulfhydryl compounds (PSH) are scavengers of reactive oxygen species [21,22] whereas protein carbonyls are produced consecutively to lipid peroxidation but essentially to glyco and protein-oxydation after oxidative stress [23]. PSH were assayed by Ellman’s test using DTNB (5,5’-Dithionitrobenzoic acid) and measured spectrophotometrically at 412 nm [24,25].…”

Section: Animals and Methodsmentioning

confidence: 99%

Nitrite enhances liver graft protection against cold ischemia reperfusion injury through a NOS independent pathway

Cherif-Sayadi

Ayed-Tka

Zaoualí

et al. 2017

Libyan Journal of Medicine

View full text Add to dashboard Cite

Introduction: Nitrite has been found to protect liver graft from cold preservation injury. However, the cell signaling pathway involved in this protection remains unclear. Here, we attempt to clarify if the NOS pathway by using the NOS inhibitor, L-NAME (L-NG-Nitroarginine methyl ester). Animals and methods: Rat livers were conserved for 24 h at 4°C in (IGL-1) solution enriched or not with nitrite at 50 nM. In a third group, rats were pretreated with 50 mg/kg of L-NAME before their liver procurement and preservation in IGL-1 supplemented with nitrite (50 nM) and L-NAME (1 mM). After 24 h of cold storage, rat livers were ex-vivo perfused at 37°C during 2 h. Control livers were perfused without cold storage. Results: Nitrite effectively protected the rat liver grafts from the onset of cold I/R injury. L-NAME treatment did not abolish the beneficial effects of nitrite. Liver damage, protein oxidation and lipid peroxidation remained at low levels in both nitrite-treated groups when compared to IGL-1 group. Antioxidant enzyme activities and functional parameters were unchanged after NOS inhibition. Conclusion: Despite NOS inhibition by L-NAME, nitrite can still provide hepatic protection during cold I/R preservation. This suggests that nitrite acts through a NOS-independent pathway.

show abstract

“…We have previously demonstrated that PGD is associated with a robust inflammatory response that promotes development of alloimmunity, autoimmunity, and chronic rejection [3, 11]. PGD has been thought to be the result of ischemia-reperfusion injury [58, 59], but this hypothesis conflicts with the recent observation that ischemic time may not correlate with PGD development [60, 61]. In other words, it is not uncommon to observe high-grade PGD development in lung allografts with very short ischemic times, or grafts with more than 8 hours of ischemia that do not develop PGD.…”

Section: Role Of Tissue-restricted Abs In Organ Transplantationmentioning

confidence: 99%

Immune Responses to Tissue-Restricted Nonmajor Histocompatibility Complex Antigens in Allograft Rejection

Bharat

Mohanakumar

2017

Journal of Immunology Research

View full text Add to dashboard Cite

Chronic diseases that result in end-stage organ damage cause inflammation, which can reveal sequestered self-antigens (SAgs) in that organ and trigger autoimmunity. The thymus gland deletes self-reactive T-cells against ubiquitously expressed SAgs, while regulatory mechanisms in the periphery control immune responses to tissue-restricted SAgs. It is now established that T-cells reactive to SAgs present in certain organs (e.g., lungs, pancreas, and intestine) are incompletely eliminated, and the dysregulation of peripheral immuneregulation can generate immune responses to SAgs. Therefore, chronic diseases can activate self-reactive lymphocytes, inducing tissue-restricted autoimmunity. During organ transplantation, donor lymphocytes are tested against recipient serum (i.e., cross-matching) to detect antibodies (Abs) against donor human leukocyte antigens, which has been shown to reduce Ab-mediated hyperacute rejection. However, primary allograft dysfunction and rejection still occur frequently. Because donor lymphocytes do not express tissue-restricted SAgs, preexisting Abs against SAgs are undetectable during conventional cross-matching. Preexisting and de novo immune responses to tissue-restricted SAgs (i.e., autoimmunity) play a major role in rejection. In this review, we discuss the evidence that supports autoimmunity as a contributor to rejection. Testing for preexisting and de novo immune responses to tissue-restricted SAgs and treatment based on immune responses after organ transplantation may improve short- and long-term outcomes after transplantation.

show abstract

Prevention of primary graft dysfunction in lung transplantation by N-acetylcysteine after prolonged cold ischemia

Cited by 32 publications

References 37 publications

Volatile Anesthetics Reduce Invasion of Colorectal Cancer Cells through Down-regulation of Matrix Metalloproteinase-9

Volatile Anesthetics Reduce Invasion of Colorectal Cancer Cells through Down-regulation of Matrix Metalloproteinase-9

Nitrite enhances liver graft protection against cold ischemia reperfusion injury through a NOS independent pathway

Immune Responses to Tissue-Restricted Nonmajor Histocompatibility Complex Antigens in Allograft Rejection

Contact Info

Product

Resources

About