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

2004 ◽  
Vol 287 (6) ◽  
pp. G1220-G1226 ◽  
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.

Albumin is not an irreplaceable carrier for amphipathic mediators of thermoregulatory responses to LPS: compensatory role of α1-acid glycoprotein

2005 ◽  
Vol 288 (4) ◽  
pp. R872-R878 ◽  
Author(s):  
Andrei I. Ivanov ◽  
Alexandre A. Steiner ◽  
Shreya Patel ◽  
Alla Y. Rudaya ◽  
Andrej A. Romanovsky
Keyword(s):  
Inflammatory Mediators ◽  
Platelet Activating Factor ◽  
Prostaglandin E ◽  
High Dose ◽  
Sprague Dawley ◽  
Acid Glycoprotein ◽  
Sprague Dawley Rats ◽  
Lps Signaling ◽  
The Brain

In view of the potential involvement of peripherally synthesized, circulating amphipathic mediators [such as platelet-activating factor (PAF) and prostaglandin E2] in the systemic inflammatory response to lipopolysaccharide (LPS), we hypothesized that transport of amphipaths by albumin is essential for conveying peripheral inflammatory signals to the brain. Our first specific aim was to test this hypothesis by studying LPS-induced fever and hypothermia in Nagase analbuminemic rats (NAR). NAR from two different colonies and normalbuminemic Sprague-Dawley rats were preimplanted with jugular catheters, and their febrile responses to a mild dose of LPS (10 μg/kg iv) at thermoneutrality and hypothermic responses to a high dose of LPS (500 μg/kg iv) in the cold were studied. NAR of both colonies developed normal febrile and hypothermic responses, thus suggesting that transport of amphipathic mediators by albumin is not indispensable for LPS signaling. Although alternative carrier proteins [such as α1-acid glycoprotein (AGP)] are known to assume transport functions of albumin in NAR, it is unknown whether inflammatory mediators are capable of inducing their actions when bound to alternative carriers. To test whether PAF, the most potent amphipathic pyrogen, causes fever when administered in an AGP-bound form was our second aim. Sprague-Dawley rats were preimplanted with jugular catheters, and their thermal responses to infusion of a 1:1 [PAF-AGP] complex (40 nmol/kg iv), AGP (40 nmol/kg iv), or various doses of free (aggregated) PAF were studied. The complex, but neither free PAF nor AGP, caused a high (∼1.5°C) fever with a short (<10 min) latency. This is the first demonstration of a pyrogenic activity of AGP-bound PAF. We conclude that, in the absence of albumin, AGP and possibly other carriers participate in immune-to-brain signaling by binding and transporting amphipathic inflammatory mediators.

Role of leukocyte beta 2-integrin in PAF-induced shock and intestinal injury

1996 ◽  
Vol 270 (1) ◽  
pp. G184-G190 ◽  
Author(s):  
X. M. Sun ◽  
X. W. Qu ◽  
W. Huang ◽  
D. N. Granger ◽  
M. Bree ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Leukocyte Adhesion ◽  
Platelet Activating Factor ◽  
Young Male ◽  
Intestinal Injury ◽  
Bowel Injury ◽  
High Dose ◽  
Sprague Dawley ◽  
Intestinal Necrosis ◽  
Beta 2

Leukocyte adhesion and diapedesis, critical steps in the inflammatory process, depend on the expression of integrin CD11b/CD18. In this study, we examined the preventive effect of monoclonal antibodies (MAb) against CD11b (1B6), CD11a, or CD18 (CL26) on platelet-activating factor (PAF)-induced bowel injury. Young male Sprague-Dawley rats were anesthetized and injected with either of two doses of PAF (2.5 or 3 micrograms/kg iv) to induce transient hypotension and irreversible shock. Some rats wee also injected intravenously with 1B6 (anti-CD11b), anti-CD11a, CL26 (anti-CD18), or combined anti-CD11a and 1B6, 30 min before PAF. Animals receiving a low dose of PAF developed mild hypotension, hemoconcentration, increased intestinal myeloperoxidase, and bowel injury after 1 h. These effects were completely prevented by pretreatment with 1B6. A high dose of PAF induced irreversible shock and gross intestinal necrosis. Both CL26 and 1B6 were partially effective in attenuating PAF-induced bowel injury. Addition of anti-CD11a to 1B6 in the treatment further ameliorated the systemic adverse effects of PAF and intestinal injury. However, focal minor injury still developed. Anti-CD11a alone, fucoidin, or anti-P-selectin was ineffective. Rats depleted of neutrophils were also largely protected from the adverse effects of PAF at high doses, although minor intestinal injury often persisted. We conclude that leukocyte beta 2-integrins play an important role in PAF-induced hypotension, leukopenia, hemoconcentration, and intestinal necrosis, and that CD11b/CD18 is the main adhesion molecule involved in the pathogenesis of injury. However, CD11/CD18- and neutrophil-independent pathways exist for mediating PAF-induced bowel injury, although their role is probably a minor one.

scholarly journals Mild DOCA-salt hypertension: sympathetic system and role of renal nerves

2011 ◽  
Vol 300 (5) ◽  
pp. H1781-H1787 ◽  
Author(s):  
Sachin S. Kandlikar ◽  
Gregory D. Fink
Keyword(s):  
Control Period ◽  
Whole Body ◽  
Renal Nerves ◽  
Experimental Hypertension ◽  
Sympathetic Activation ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Salt Hypertension ◽  
Hypertension Development

Excess sympathetic nervous system activity (SNA) is linked to human essential and experimental hypertension. To test whether sympathetic activation is associated with a model of deoxycorticosterone acetate (DOCA)-salt hypertension featuring two kidneys and a moderate elevation of blood pressure, we measured whole body norepinephrine (NE) spillover as an index of global SNA. Studies were conducted in chronically catheterized male Sprague-Dawley rats drinking water containing 1% NaCl and 0.2% KCl. After a 7-day surgical recovery and a 3-day control period, a DOCA pellet (50 mg/kg) was implanted subcutaneously in one group of rats (DOCA), while the other group underwent sham implantation (Sham). NE spillover was measured on control day 2 and days 7 and 14 after DOCA administration or sham implantation. During the control period, mean arterial pressure (MAP) was similar in Sham and DOCA rats. MAP was significantly increased in the DOCA group compared with the Sham group after DOCA administration ( day 14: Sham = 109 ± 5.3, DOCA = 128 ± 3.6 mmHg). However, plasma NE concentration, clearance, and spillover were not different in the two groups at any time. To determine whether selective sympathetic activation to the kidneys contributes to hypertension development, additional studies were performed in renal denervated (RDX) and sham-denervated (Sham-DX) rats. MAP, measured by radiotelemetry, was similar in both groups during the control and DOCA treatment periods. In conclusion, global SNA is not increased during the development of mild DOCA-salt hypertension, and fully intact renal nerves are not essential for hypertension development in this model.

Chronic intravenous administration of V1 arginine vasopressin agonist results in sustained hypertension

1994 ◽  
Vol 267 (2) ◽  
pp. H751-H756 ◽  
Author(s):  
A. W. Cowley ◽  
E. Szczepanska-Sadowska ◽  
K. Stepniakowski ◽  
D. Mattson
Keyword(s):  
Body Weight ◽  
Arginine Vasopressin ◽  
Plasma Catecholamines ◽  
Plasma Osmolality ◽  
Sprague Dawley ◽  
Prolonged Administration ◽  
Chronic Stimulation ◽  
Sustained Hypertension ◽  
Sprague Dawley Rats

Despite the well-recognized vasoconstrictor and fluid-retaining actions of vasopressin, prolonged administration of arginine vasopressin (AVP) to normal animals or humans fails to produce sustained hypertension. The present study was performed to elucidate the role of the V1 receptor in determining the ability of AVP to produce sustained hypertension. Conscious Sprague-Dawley rats with implanted catheters were infused with the selective V1 agonist, [Phe2,Ile3,Orn8]vasopressin (2 ng.kg-1.min-1), for 14 days in amounts that were acutely nonpressor. Blood pressure (MAP), heart rate (HR), body weight, and water intake (WI) were determined daily. Plasma AVP, plasma catecholamines norepinephrine and epinephrine, plasma osmolality, and electrolyte concentration were determined before and on days 1 and 7 of infusion. MAP increased significantly by 10.4 +/- 4.5 mmHg on day 1 and rose to 22 +/- 5 mmHg above control by day 14 (transient decrease on days 6-9) and then fell to control levels after the infusion was stopped. HR did not change significantly. Plasma AVP immunoreactivity increased from 2.5 +/- 0.3 to 10.9 +/- 2.1 pg/ml, whereas norepinephrine tended to fall only on day 1, with epinephrine only slightly elevated on day 7. No evidence of fluid retention was found, and rats lost sodium only on the first day of V1 agonist infusion. Body weight increased throughout the study but was unrelated to the changes of MAP. We conclude that chronic stimulation of V1 receptors results in sustained hypertension in rats.

The Hepatoprotective Role of Warburgia salutaris and Iso-Mukaadial Acetate on Carbon tetrachloride Intoxicated Rats Model

2021 ◽  
Vol 17 ◽  
Author(s):  
Gideon Ayeni ◽  
Mthokozisi Blessing Cedric Simelane ◽  
Shahidul Islam ◽  
Ofentse Jacob Pooe
Keyword(s):  
Carbon Tetrachloride ◽  
Hepatic Injury ◽  
Antioxidant Properties ◽  
Hepatic Necrosis ◽  
Protective Role ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Isolated Compound

Background: Medicinal plants together with their isolated bioactive compounds are known for their antioxidant properties which constitute therapeutic agents that are routinely employed in the treatment of liver diseases. Aims of the Study: The current study sought to explore the protective role of Warburgia salutaris and its isolated compound, iso-mukaadial acetate against carbon tetrachloride (CCl4)-induced hepatic injury. Methods: Thirty-five male Sprague Dawley rats were divided into seven groups of five animals each and injected with CCl4 to induce hepatic injury. Results: Treatment with the crude extract of W. salutaris and of iso-mukaadial acetate significantly reduced the levels of alkaline phosphatase, alanine and aspartate aminotransaminases, total bilirubin and malondialdehyde in a dose dependent manner, when compared to untreated groups. Liver histology revealed a reduction in hepatic necrosis and inflammation. Conclusion: The current investigation has demonstrated that W. salutaris extract and iso-mukaadial acetate could mitigate the acute liver injury inflicted by a hepatotoxic inducer in rats.

scholarly journals Transient Neonatal Cryptosporidium parvum Infection Triggers Long-Term Jejunal Hypersensitivity to Distension in Immunocompetent Rats

2006 ◽  
Vol 74 (7) ◽  
pp. 4387-4389 ◽  
Author(s):  
Rachel Marion ◽  
Asiya Baishanbo ◽  
Gilles Gargala ◽  
Arnaud François ◽  
Philippe Ducrotté ◽  
...  
Keyword(s):  
Cryptosporidium Parvum ◽  
Myeloperoxidase Activity ◽  
Sprague Dawley ◽  
Depressor Response ◽  
Sprague Dawley Rats

ABSTRACT In 5-day-old immunocompetent Sprague-Dawley rats infected with either 102 or 105 Cryptosporidium parvum oocysts, transient infection resulted 120 days later in increased cardiovascular depressor response to jejunal distension and jejunal myeloperoxidase activity (P < 0.05). Nitazoxanide treatment normalized jejunal sensitivity (P < 0.001) but not myeloperoxidase levels (P > 0.05). Data warrant further evaluation of the role of early cryptosporidiosis in the development of chronic inflammatory gut conditions.

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