The Role of Luminal Nutrients in Intestinal Injury from Mesenteric Reperfusion and Platelet-Activating Factor in the Developing Rat

We previously showed that group II phospholipase A2(PLA2-II), a secretory, bactericidal, and proinflammatory protein in intestinal crypts, is upregulated after lipopolysaccharide (LPS) and platelet-activating factor (PAF) challenge. Here we examined whether germ-free environment (GF) or antibiotic treatment (ABX) affects the pathophysiological responses and intestinal PLA2-II activity after PAF (1.5 μg/kg) or LPS (8 mg/kg) injection. We found that LPS and PAF induced hypotension and mild intestinal injury in conventionally fed (CN) rats; these changes were milder in ABX rats, whereas GF rats showed no intestinal injury. PLA2-II enzyme activity was detected in normal rat small intestine; the basal level was not diminished in ABX or GF rats. PAF and LPS caused an increase in PLA2-II activity, which was abrogated in GF and ABX rats. Recolonization of GF rats by enteral contamination restituted their PLA2-II response to PAF and LPS and susceptibility to bowel injury. We conclude that PAF- and LPS-induced increases in PLA2-II activity are dependent on gut bacteria, and ABX and GF rats are less susceptible to LPS-induced injury than CN rats.

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The role of xanthine oxidase in platelet activating factor induced intestinal injury in the rat

Gut ◽

10.1136/gut.44.2.203 ◽

1999 ◽

Vol 44 (2) ◽

pp. 203-211 ◽

Cited By ~ 25

Author(s):

X W Qu ◽

R A Rozenfeld ◽

W Huang ◽

G B Bulkley ◽

W Hsueh

Keyword(s):

Xanthine Oxidase ◽

Platelet Activating Factor ◽

Total Activity ◽

Histochemical Staining ◽

Polymorphonuclear Leucocyte ◽

Intestinal Injury ◽

High Dose ◽

Neutrophil Sequestration ◽

Intestinal Necrosis

BackgroundXanthine oxidase (XO) is an important source of reactive oxygen species in the small intestine.AimsTo examine the interaction of platelet activating factor (PAF), XO, and neutrophils in mediating intestinal injury in rats.MethodsTwo doses of PAF were used to induce either reversible hypotension, or irreversible shock with intestinal necrosis. The activities of XO, and its precursor xanthine dehydrogenase (XD), in both the whole intestinal tissue and epithelial cells, were measured. XO was localised by histochemical staining.ResultsPAF dose dependently induced an increase in XO activity, predominantly in the ileal epithelium, without altering the total activity of XD+XO. Most of the XD to XO conversion was via proteolysis. PAF induced XO activation and intestinal injury were prevented by prior neutrophil depletion. PAF induced XO activation is probably not due to reperfusion, as XO activation preceded the recovery of mesenteric flow. Allopurinol pretreatment substantially inhibited intestinal neutrophil sequestration induced by high dose (but not low dose) PAF.ConclusionsPAF rapidly activates intestinal XO through proteolytic XD-XO conversion, predominantly in the ileal epithelium. This effect is mediated by neutrophils. XO activation promotes PAF induced polymorphonuclear leucocyte sequestration in the intestine.

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Macrophage inflammatory protein-2 mediates the bowel injury induced by platelet-activating factor

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00231.2004 ◽

2004 ◽

Vol 287 (6) ◽

pp. G1220-G1226 ◽

Cited By ~ 20

Author(s):

Xin-Bing Han ◽

Xueli Liu ◽

Wei Hsueh ◽

Isabelle G. De Plaen

Keyword(s):

Platelet Activating Factor ◽

Intestinal Injury ◽

Bowel Injury ◽

Second Step ◽

Sprague Dawley ◽

Inflammatory Protein ◽

Sprague Dawley Rats ◽

Rabbit Igg ◽

Macrophage Inflammatory Protein

Platelet-activating factor (PAF) is a potent endogenous mediator of bowel inflammation. It activates neutrophils that are needed to initiate the inflammatory response. Macrophage inflammatory protein-2 (MIP-2), a critical C-X-C chemokine secreted by macrophages and epithelial cells, is a potent chemoattractant for neutrophils. Whereas MIP-2 has been previously shown to mediate the injury in various organs, its role in acute intestinal injury has never been assessed. In this study, we first investigated the effect of PAF on MIP-2 expression in the intestine. Anesthetized young adult male Sprague-Dawley rats were injected intravenously with either PAF (1.5 μg/kg) or saline. Sixty minutes later, ileal MIP-2 gene expression was determined by semiquantitative RT-PCR, and plasma and ileal MIP-2 protein was determined by ELISA. In a second step, we assessed the role of MIP-2 in PAF-induced bowel injury. Rats were pretreated with rabbit anti-rat MIP-2 antibodies or control IgG for 90 min and then injected intravenously with PAF (2.5 μg/kg) for 90 min. We found that, in the rat intestine, 1) MIP-2 mRNA was only minimally expressed constitutively in sham-operated animals; 2) MIP-2 mRNA was significantly upregulated in response to PAF; 3) MIP-2 protein plasma levels and local production of MIP-2 in the ileum were markedly induced by PAF; 4) the administration of anti-rat MIP-2 IgG, but not control rabbit IgG, markedly reduced PAF-induced bowel injury (injury scores of 0.19 ± 0.09 vs. 1.12 ± 0.43, P < 0.05), hypotension, and leukopenia but did not reduce PAF-induced hemoconcentration. Thus we conclude that MIP-2 mediates PAF-induced intestinal injury.

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The Role of Platelet-Activating Factor in Endothelial Cells

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647261 ◽

1990 ◽

Vol 64 (01) ◽

pp. 099-103 ◽

Cited By ~ 39

Author(s):

Stephen M Prescott ◽

Thomas M McIntyre ◽

Guy A Zimmerman

Keyword(s):

Endothelial Cells ◽

Platelet Activating Factor

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Faculty Opinions recommendation of Role of Aquaporin-3 in Intestinal Injury Induced by Sepsis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.737303750.793572609 ◽

2020 ◽

Author(s):

Wendy Bollag

Keyword(s):

Intestinal Injury ◽

Aquaporin 3

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Lack of Platelet-Activating Factor Receptor Attenuates Experimental Food Allergy but Not Its Metabolic Alterations regarding Adipokine Levels

BioMed Research International ◽

10.1155/2016/8601359 ◽

2016 ◽

Vol 2016 ◽

pp. 1-10 ◽

Cited By ~ 4

Author(s):

Nathália Vieira Batista ◽

Roberta Cristelli Fonseca ◽

Denise Perez ◽

Rafaela Vaz Sousa Pereira ◽

Juliana de Lima Alves ◽

...

Keyword(s):

Adipose Tissue ◽

Food Allergy ◽

Inflammatory Process ◽

Platelet Activating Factor ◽

Oral Challenge ◽

Tissue Loss ◽

Lack Of Information ◽

Paf Receptor ◽

Rolling Leukocytes

Platelet-activating factor (PAF) is known to be an important mediator of anaphylaxis. However, there is a lack of information in the literature about the role of PAF in food allergy. The aim of this work was to elucidate the participation of PAF during food allergy development and the consequent adipose tissue inflammation along with its alterations. Our data demonstrated that, both before oral challenge and after 7 days receiving ovalbumin (OVA) diet, OVA-sensitized mice lacking the PAF receptor (PAFR) showed a decreased level of anti-OVA IgE associated with attenuated allergic markers in comparison to wild type (WT) mice. Moreover, there was less body weight and adipose tissue loss in PAFR-deficient mice. However, some features of inflamed adipose tissue presented by sensitized PAFR-deficient and WT mice after oral challenge were similar, such as a higher rate of rolling leukocytes in this tissue and lower circulating levels of adipokines (resistin and adiponectin) in comparison to nonsensitized mice. Therefore, PAF signaling through PAFR is important for the allergic response to OVA but not for the adipokine alterations caused by this inflammatory process. Our work clarifies some effects of PAF during food allergy along with its role on the metabolic consequences of this inflammatory process.

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The role of sympathetic innervation in the developing rat gubernaculum

Journal of Pediatric Surgery ◽

10.1016/j.jpedsurg.2006.10.037 ◽

2007 ◽

Vol 42 (2) ◽

pp. 350-354

Author(s):

Yasunari Sasaki ◽

John M. Hutson ◽

Melanie C.C. Clarke

Keyword(s):

Sympathetic Innervation ◽

Developing Rat

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Role of Platelet-Activating Factor in Cardiovascular Pathophysiology

Physiological Reviews ◽

10.1152/physrev.2000.80.4.1669 ◽

2000 ◽

Vol 80 (4) ◽

pp. 1669-1699 ◽

Cited By ~ 245

Author(s):

Giuseppe Montrucchio ◽

Giuseppe Alloatti ◽

Giovanni Camussi

Keyword(s):

Cardiovascular System ◽

Cell Biology ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Critical Role ◽

Experimental Studies ◽

Platelet Activating Factor ◽

Biologically Active ◽

Endothelial Cell Migration

Platelet-activating factor (PAF) is a phospholipid mediator that belongs to a family of biologically active, structurally related alkyl phosphoglycerides. PAF acts via a specific receptor that is coupled with a G protein, which activates a phosphatidylinositol-specific phospholipase C. In this review we focus on the aspects that are more relevant for the cell biology of the cardiovascular system. The in vitro studies provided evidence for a role of PAF both as intercellular and intracellular messenger involved in cell-to-cell communication. In the cardiovascular system, PAF may have a role in embryogenesis because it stimulates endothelial cell migration and angiogenesis and may affect cardiac function because it exhibits mechanical and electrophysiological actions on cardiomyocytes. Moreover, PAF may contribute to modulation of blood pressure mainly by affecting the renal vascular circulation. In pathological conditions, PAF has been involved in the hypotension and cardiac dysfunctions occurring in various cardiovascular stress situations such as cardiac anaphylaxis and hemorrhagic, traumatic, and septic shock syndromes. In addition, experimental studies indicate that PAF has a critical role in the development of myocardial ischemia-reperfusion injury. Indeed, PAF cooperates in the recruitment of leukocytes in inflamed tissue by promoting adhesion to the endothelium and extravascular transmigration of leukocytes. The finding that human heart can produce PAF, expresses PAF receptor, and is sensitive to the negative inotropic action of PAF suggests that this mediator may have a role also in human cardiovascular pathophysiology.

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