scholarly journals Role of xanthine oxidase and granulocytes in ischemia-reperfusion injury

1988 ◽  
Vol 255 (6) ◽  
pp. H1269-H1275 ◽  
Author(s):  
D. N. Granger
Keyword(s):  
Hydrogen Peroxide ◽  
Xanthine Oxidase ◽  
Superoxide Anion ◽  
Cell Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Microvascular Endothelium ◽  
Ischemic Period ◽  
Membrane Components

In this lecture, evidence is presented to support the following hypothesis regarding the roles of xanthine oxidase-derived oxidants and granulocytes in ischemia-reperfusion-induced microvascular injury. During the ischemic period, ATP is catabolized to yield hypoxanthine. The hypoxic stress also triggers the conversion of NAD-reducing xanthine dehydrogenase to the oxygen radical-producing xanthine oxidase. During reperfusion, molecular oxygen is reintroduced into the tissue where it reacts with hypoxanthine and xanthine oxidase to produce a burst of superoxide anion and hydrogen peroxide. In the presence of iron, superoxide anion and hydrogen peroxide react via the Haber-Weiss reaction to form hydroxyl radicals. This highly reactive and cytotoxic radical then initiates lipid peroxidation of cell membrane components and the subsequent release of substances that attract, activate, and promote the adherence of granulocytes to microvascular endothelium. The adherent granulocytes then cause further endothelial cell injury via the release of superoxide and various proteases.

Injury of the renal microvascular endothelium alters barrier function after ischemia

2003 ◽  
Vol 285 (2) ◽  
pp. F191-F198 ◽  
Author(s):  
Timothy A. Sutton ◽  
Henry E. Mang ◽  
Silvia B. Campos ◽  
Ruben M. Sandoval ◽  
Mervin C. Yoder ◽  
...  
Keyword(s):  
Cell Injury ◽  
Ischemia Reperfusion Injury ◽  
Morphological Changes ◽  
Ischemia Reperfusion ◽  
Endothelial Injury ◽  
Microvascular Endothelial Cell ◽  
Vascular Endothelial ◽  
Microvascular Endothelium ◽  
Renal Microvasculature ◽  
Microvascular Endothelial

The role of renal microvascular endothelial cell injury in the pathophysiology of ischemic acute renal failure (ARF) remains largely unknown. No consistent morphological alterations have been ascribed to the endothelium of the renal microvasculature as a result of ischemia-reperfusion injury. Therefore, the purpose of this study was to examine biochemical markers of endothelial injury and morphological changes in the renal microvascular endothelium in a rodent model of ischemic ARF. Circulating von Willebrand factor (vWF) was measured as a marker of endothelial injury. Twenty-four hours after ischemia, circulating vWF peaked at 124% over baseline values ( P = 0.001). The FVB-TIE2/GFP mouse was utilized to localize morphological changes in the renal microvascular endothelium. Immediately after ischemia, there was a marked increase in F-actin aggregates in the basal and basolateral aspect of renal microvascular endothelial cells in the corticomedullary junction. After 24 h of reperfusion, the pattern of F-actin staining was more similar to that observed under physiological conditions. In addition, alterations in the integrity of the adherens junctions of the renal microvasculature, as demonstrated by loss of localization in vascular endothelial cadherin immunostaining, were observed after 24 h of reperfusion. This observation temporally correlated with the greatest extent of permeability defect in the renal microvasculature as identified using fluorescent dextrans and two-photon intravital imaging. Taken together, these findings indicate that renal vascular endothelial injury occurs in ischemic ARF and may play an important role in the pathophysiology of ischemic ARF.

Role of xanthine oxidase and eicosanoids in development of pancreatic ischemia-reperfusion injury

Inflammation ◽  
1995 ◽  
Vol 19 (4) ◽  
pp. 469-478 ◽  
Author(s):  
G. Hotter ◽  
D. Closa ◽  
E. Gelp� ◽  
N. Prats ◽  
J. Rosell�-Catafau
Keyword(s):  
Reperfusion Injury ◽  
Xanthine Oxidase ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Pancreatic Ischemia

scholarly journals The Role of IL-33 in Experimental Heart Transplantation

2020 ◽  
Vol 2020 ◽  
pp. 1-7 ◽  
Author(s):  
Jie Chen ◽  
Yan He ◽  
Zhongming Xie ◽  
Yingying Wei ◽  
Lihua Duan
Keyword(s):  
Heart Transplantation ◽  
Graft Rejection ◽  
Cell Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Solid Organ Transplantation ◽  
Cell Types ◽  
Solid Organ ◽  
Interleukin 33

Interleukin-33 (IL-33) is a member of the IL-1 family of proteins that are produced by a variety of cell types in multiple tissues. Under conditions of cell injury or death, IL-33 is passively released from the nucleus and acts as an “alarmin” upon binding to its specific receptor ST2, which leads to proinflammatory or anti-inflammatory effects depending on the pathological environment. To date, numerous studies have investigated the roles of IL-33 in human and murine models of diseases of the nervous system, digestive system, pulmonary system, as well as other organs and systems, including solid organ transplantation. With graft rejection and ischemia-reperfusion injury being the most common causes of grafted organ failure or dysfunction, researchers have begun to investigate the role of IL-33 in the immune-related mechanisms of graft tolerance and rejection using heart transplantation models. In the present review, we summarize the identified roles of IL-33 as well as the corresponding mechanisms by which IL-33 acts within the progression of graft rejection after heart transplantation in animal models.

Role of xanthine oxidase in reperfusion injury of ischemic skeletal muscles in the pig and human

1993 ◽  
Vol 75 (1) ◽  
pp. 246-255 ◽  
Author(s):  
D. Dorion ◽  
A. Zhong ◽  
C. Chiu ◽  
C. R. Forrest ◽  
B. Boyd ◽  
...  
Keyword(s):  
Uric Acid ◽  
Reperfusion Injury ◽  
Xanthine Oxidase ◽  
Acid Content ◽  
Skeletal Muscles ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Warm Ischemia ◽  
Muscle Necrosis

We investigated whether xanthine oxidase (XO) is a major source of oxygen-derived free radicals (oxy-radicals) in the pig and human skeletal muscles. It was observed that xanthine dehydrogenase and XO activities in nonischemic pig latissimus dorsi (LD) and gracilis muscles and human LD and rectus abdominis (RA) muscles were < 0.5 mU/g wet wt. The pig LD muscle hypoxanthine content increased significantly from 0.33 +/- 0.02 to 2.33 +/- 0.44 mumol/g dry wt after 5 h of warm ischemia, but the muscle uric acid content remained unchanged up to 2 h of reperfusion. Similarly, the hypoxanthine content in the human LD and RA muscles increased from 0.33 +/- 0.03 to 0.84 +/- 0.23 mumol/g dry wt after 2.0–3.5 h of warm ischemia, and the muscle uric acid content remained unchanged at the end of 15–90 min of reperfusion. Furthermore, 5 days of allopurinol treatment (25 mg/kg iv twice daily) starting 2 days before ischemia or 3 days of oxypurinol treatment (25 mg/kg iv twice daily) starting 15 min before reperfusion did not attenuate the extent of skeletal muscle necrosis in pig LD muscles subjected to 5 h of ischemia and 48 h of reperfusion. However, deferoxamine treatment (250 mg/kg iv twice daily) starting before or after ischemia, as described above, significantly reduced the extent of pig LD muscle necrosis. Finally, at 2 and 48 h of reperfusion significantly higher muscle neutrophil contents were seen in ischemic than in nonischemic control pig LD muscles. Neutrophil depletion with mechlorethamine (0.75 mg/kg iv) significantly reduced the extent of necrosis in pig LD muscles. These observations indicate that XO is not a major source of oxy-radicals in ischemia/reperfusion injury in the pig gracilis and LD muscles and human RA and LD muscles.

Role of calcium-independent phospholipase A2 in complement-mediated glomerular epithelial cell injury

2008 ◽  
Vol 294 (3) ◽  
pp. F469-F479 ◽  
Author(s):  
Daniel Cohen ◽  
Joan Papillon ◽  
Lamine Aoudjit ◽  
Hongping Li ◽  
Andrey V. Cybulsky ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Cell Injury ◽  
Ischemia Reperfusion Injury ◽  
Morphological Changes ◽  
Ischemia Reperfusion ◽  
Prostaglandin E ◽  
Glomerular Epithelial Cell ◽  
Novel Approach

In experimental membranous nephropathy, complement C5b-9-induced glomerular epithelial cell (GEC) injury leads to morphological changes in GEC and proteinuria, in association with phospholipase A2 (PLA2) activation. The present study addresses the role of calcium-independent PLA2 (iPLA2) in GEC injury. iPLA2β short and iPLA2γ were expressed in cultured rat GEC and normal rat glomeruli. To determine whether iPLA2 is involved in complement-mediated arachidonic acid (AA) release, GEC were stably transfected with iPLA2γ or iPLA2β cDNAs (GEC-iPLA2γ; GEC-iPLA2β). Compared with control cells (GEC-Neo), GEC-iPLA2γ and GEC-iPLA2β demonstrated greater expression of iPLA2 proteins and activities. Complement-mediated release of [3H]AA was augmented significantly in GEC-iPLA2γ compared with GEC-Neo, and the augmented [3H]AA release was inhibited by the iPLA2-directed inhibitor bromoenol lactone (BEL). For comparison, overexpression of iPLA2γ also amplified [3H]AA release after incubation of GEC with H2O2, or chemical anoxia followed by reexposure to glucose (in vitro ischemia-reperfusion injury). In parallel with release of [3H]AA, complement-mediated production of prostaglandin E2 was amplified in GEC-iPLA2γ. Complement-mediated cytotoxicity was attenuated significantly in GEC-iPLA2γ compared with GEC-Neo, and the cytoprotective effect of iPLA2γ was reversed by BEL, and in part by indomethacin. Overexpression of iPLA2β did not amplify complement-dependent [3H]AA release, but nonetheless attenuated complement-mediated cytotoxicity. Thus iPLA2γ may be involved in complement-mediated release of AA. Expression of iPLA2γ or iPLA2β induces cytoprotection against complement-dependent GEC injury. Modulation of iPLA2 activity may prove to be a novel approach to reducing GEC injury.

1843: Role of Cxcr2 in Renal Ischemia/Reperfusion Injury

2004 ◽  
Vol 171 (4S) ◽  
pp. 487-487
Author(s):  
Motoo Araki ◽  
Masayoshi Miura ◽  
Hiromi Kumon ◽  
John Belperio ◽  
Robert Strieter ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Renal Ischemia Reperfusion Injury
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