Roles of Platelet-Activating Factor, Interleukin-1β and Interleukin-6 in Intestinal Barrier Dysfunction Induced by Mesenteric Arterial Ischemia and Reperfusion

Sun, Zhengwu; Wang, Xiangdong; Lasson, Åke; Börjesson, Anna; Leveau, Per; Haraldsen, Pernille; Andersson, Roland

doi:10.1006/jsre.1999.5746

Cited by 49 publications

(34 citation statements)

References 26 publications

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“…A number of chemical and cellular mediators, including reactive oxygen species (Zimmerman & Granger, 1994), platelet-activating factor Sun et al, 2000), cytokines (tumour necrosis factor-a (TNF-a) and interleukin-6) (Sorkine et al, 1995;Yao et al, 1996;Sun et al, 1999), mucosal mast cells (Kanwar & Kubes, 1994;Kanwar et al, 1998) and polymorphonuclear leukocytes (PMNs) (Hernandez et al, 1987;Sisley et al, 1994;Koike et al, 1995) have been implicated in the pathogenesis of intestinal I/R. In addition, activation of the complement system, which results in production of the biologically active anaphylatoxins, complement factors 3a (C3a), 4a and 5a (C5a), has been demonstrated to play a significant role in the pathology of I/R (Riedemann & Ward, 2003).…”

Section: Introductionmentioning

confidence: 99%

Comparative anti‐inflammatory activities of antagonists to C3a and C5a receptors in a rat model of intestinal ischaemia/reperfusion injury

Proctor

Shiels

Reid

et al. 2004

British J Pharmacology

101

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1 Complement activation is implicated in the pathogenesis of intestinal ischaemia-reperfusion injury (I/R), although the relative importance of individual complement components is unclear. A C3a receptor antagonist N(2)-[(2,2-diphenylethoxy)acetyl]-L-arginine (C3aRA) has been compared with a C5a receptor antagonist (C5aRA), AcF-[OPdChaWR], in a rat model of intestinal I/R. 2 C3aRA (IC 50 ¼ 0.15 mM) and C5aRA (IC 50 ¼ 0.32 mM) bound selectively to human polymorphonuclear leukocyte (PMN) C3a and C5a receptors, respectively. Effects on circulating neutrophils and blood pressure in the rat were also assessed. 3 Anaesthetised rats, subjected to intestinal ischaemia (30 min) and reperfusion (120 min), were administered intravenously with either (A) the C3aRA (0.1-1.0 mg kg À1 ); the C5aRA (1.0 mg kg À1 ); the C3aRA þ C5aRA (each 1.0 mg kg À1 ); or vehicle, 45 min prior, or (B) the C3aRA (1.0 mg kg À1 ) or vehicle, 120 min prior to reperfusion. 4 The C3aRA and C5aRA, administered 45 min prior to reperfusion, displayed similar efficacies at ameliorating several disease markers (increased oedema, elevated ALT levels and mucosal damage) of rat intestinal I/R. The combination drug treatment did not result in greater injury reduction than either antagonist alone. However, doses of the C3aRA (0.01-10 mg kg À1 ) caused transient neutropaenia, and the highest dose (10 mg kg À1 ) also caused a rapid and transient hypertension. 5 The C3aRA (1.0 mg kg À1 ), delivered 120 min prior to reperfusion to remove the global effect of C3aRA-induced neutrophil sequestration, did not attenuate the markers of intestinal I/R, despite persistent C3aR antagonism at this time. 6 C3aR antagonism does not appear to be responsible for the anti-inflammatory actions of this C3aRA in intestinal I/R in the rat. Instead, C3aRA-mediated global neutrophil tissue sequestration during ischaemia and early reperfusion may account for the protective effects observed.

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Section: Introductionmentioning

confidence: 99%

Comparative anti‐inflammatory activities of antagonists to C3a and C5a receptors in a rat model of intestinal ischaemia/reperfusion injury

Proctor

Shiels

Reid

et al. 2004

British J Pharmacology

101

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“…GI/R causes gut dysfunction characterized by histological evidence of impaired gut motility, increased intestinal permeability, and mucosal injury (18). Numerous mediators have been implicated in GI/R injury, including cytokines (8,15,43,54,55) NF-B is maintained in a latent form in the cytoplasm of cells where it is complexed to inhibitory factor-B (I B) proteins (24). Upon activation of NF-B, I B is phosphorylated (p) by I B kinases at two conserved serine residues in the NH 2 terminus, which targets the protein for ubiquination and degradation by the proteosome.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Role for complement in mediating intestinal nitric oxide synthase-2 and superoxide dismutase expression

Montalto

Hart

Jordan

et al. 2003

American Journal of Physiology-Gastrointestinal and Liver Physi

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. Role for complement in mediating intestinal nitric oxide synthase-2 and superoxide dismutase expression. Am J Physiol Gastrointest Liver Physiol 285: G197-G206, 2003. First published March 13, 2003 10.1152/ajpgi.00029.2003.-Inducible nitric oxide synthase (iNOS) and superoxide dismutase (SOD) play an important role in the pathology of ischemia-reperfusion. This study sought to determine if the proinflammatory effects of complement modulate iNOS and SOD in the rat after gastrointestinal ischemia and reperfusion (GI/R). An inhibitory or noninhibitory anti-complement component 5 (C5) monoclonal antibody (18A or 16C, respectively) was administered before GI/R. RT-PCR revealed a significant increase in intestinal iNOS mRNA compared with sham after GI/R that was attenuated significantly by 18A. Immunohistochemistry demonstrated increased iNOS protein expression within the intestinal crypts after GI/R. Cu/Zn SOD (mRNA and protein) was unaffected by GI/R, whereas Cu/Zn SOD activity was reduced significantly. Mn SOD protein expression was decreased significantly by GI/R. Anti-C5 preserved Cu/Zn SOD activity and Mn SOD protein expression. Staining for nitrotyrosine showed that anti-C5 treatment reduced protein nitration in the reperfused intestine. Immunohistochemistry demonstrated prominent phosphorylated (p) inhibitory factor-B (I B)-␣ staining of intestinal tissue after GI/R, whereas anti-C5 reduced p-I B-␣ expression. These data indicate that complement may mediate tissue damage during GI/R by increasing intestinal iNOS and decreasing the activity and protein levels of Cu/Zn SOD and Mn SOD, respectively. ischemia-reperfusion; inhibitory factor-B; interleukin-1␤ GASTROINTESTINAL ISCHEMIA-reperfusion (GI/R) is a common clinical problem in the settings of sepsis, hemorrhagic shock, vascular surgery, and small bowel transplantation (17, 21). GI/R causes gut dysfunction characterized by histological evidence of impaired gut motility, increased intestinal permeability, and mucosal injury (18). Numerous mediators have been implicated in GI/R injury, including cytokines (8,15,43,54,55) NF-B is maintained in a latent form in the cytoplasm of cells where it is complexed to inhibitory factor-B (I B) proteins (24). Upon activation of NF-B, I B is phosphorylated (p) by I B kinases at two conserved serine residues in the NH 2 terminus, which targets the protein for ubiquination and degradation by the proteosome. This rapidly frees NF-B to translocate to the nucleus, where it upregulates the transcription of a variety of adhesion molecules (ICAM-1 and VCAM-1), cytokines (TNF, IL-1, and IL-6), and enzymes (iNOS; see Refs. 24 and 37).NO has been implicated as a mediator of tissue damage in several models of intestinal disease, including reperfusion injury (26,47,48). NO can be produced by three nitric oxide synthase (NOS) isoforms (neuronal NOS, iNOS, and endothelial NOS). Specific inhibition of iNOS has been shown to attenuate NO production significantly and decrease intestinal injury, indicating that iNOS mediates the excessive p...

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“…[24] Furthermore, intestinal I/R triggers accumulation of cytokines, platelet activating factor, IL-1β, IL-6 and NO. [25,26] Previous studies [27,28] found mitochondrial damage in the intestinal I/R model, confirming that impaired intestinal mitochondria result in morphological changes and changes of respiratory function. The administration of oxygen saturated solution to the intestine may partially restore mitochondrial function.…”

Section: Discussionmentioning

confidence: 62%

Effects of hyperbaric oxygen on intestinal mucosa apoptosis caused by ischemia-reperfusion injury in rats

Zhou¹,

Sun²,

Wang³

2012

World Journal of Emergency Medicine

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Roles of Platelet-Activating Factor, Interleukin-1β and Interleukin-6 in Intestinal Barrier Dysfunction Induced by Mesenteric Arterial Ischemia and Reperfusion

Cited by 49 publications

References 26 publications

Comparative anti‐inflammatory activities of antagonists to C3a and C5a receptors in a rat model of intestinal ischaemia/reperfusion injury

Comparative anti‐inflammatory activities of antagonists to C3a and C5a receptors in a rat model of intestinal ischaemia/reperfusion injury

Role for complement in mediating intestinal nitric oxide synthase-2 and superoxide dismutase expression

Effects of hyperbaric oxygen on intestinal mucosa apoptosis caused by ischemia-reperfusion injury in rats

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