Evidence that mast cell degranulation, histamine and tumour necrosis factor α release occur in LPS‐induced plasma leakage in rat skin

Iuvone, Teresa; Bossche, R. van den; D’Acquisto, Fulvio; Carnuccio, Rosa; Herman, Arnold G.

doi:10.1038/sj.bjp.0702828

Cited by 40 publications

(33 citation statements)

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“…Because LT induces a cytokine-independent, shock-like death in mice and rats, we hypothesized that anaphylactic shock-like events due to mast cell degranulation or release of histamine from other cells could be the cause of LT-mediated vascular leakage and shock (26,39). To test this hypothesis, we utilized the drug ketotifen, which inhibits mast cell, basophil, and eosinophil degranulation and interferes with histamine function (14), protecting against shock (2, 35) and inhibiting LPS-mediated leakage by preventing mast cell degranulation, in a Miles assay (18,19). Ketotifen or saline (control) was introduced to mice systemically by i.p.…”

Section: Resultsmentioning

confidence: 99%

“…Fischer 344 rats were purchased from Taconic Farms (Germantown, NY) and used at weights of 150 to 180 g. Rats were injected intravenously (i.v.) in the tail vein with 12 g LT, which has been shown by our studies to result in death within 60 min (unpublished observations) with or without 250 g of the mast cell stabilizer drug ketotifen (18,19), and monitored for the exact time to death.…”

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Anthrax Lethal Toxin Induces Ketotifen-Sensitive Intradermal Vascular Leakage in Certain Inbred Mice

et al. 2006

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Bacillus anthracis lethal toxin (LT) is a bipartite toxin composed of protective antigen (PA) and lethal factor (LF). Injection of LT produces clinical signs characteristic of anthrax infection, including pleural edema and vascular collapse in various animal models. We utilized the classic Miles leakage assay to quantify vascular leakage in mice. LT injected intradermally induced leakage as early as 15 to 25 min in some inbred mouse strains, but not in others, whereas PA or LF individually did not induce leakage. A third component of anthrax toxin, edema factor, did not induce leakage alone or with PA. Leakage was quantified in eight mouse strains, and no correlation was found between sensitivity to intradermal leakage and sensitivity to the lethality of systemically administered LT. The leakage could be inhibited by ketotifen, an inhibitor of mast cell degranulation, but not by azelastine, a histamine receptor 1 antagonist, or by ketanserin, a serotonin 5-HT2A receptor antagonist. LT was cytotoxic to MC/9 mast cells (in vitro) by 7 h after toxin treatment but did not induce histamine release from these cells. Mast cell-deficient mice exhibited the leakage event and had no increased resistance to systemic LT. Human umbilical vein endothelial cells were resistant to LT over 12 h, with only 20% of cells succumbing by 24 h, suggesting that endothelial cell killing is not the cause of the rapid LT-mediated leakage event. We describe here a ketotifen-sensitive vascular leakage event induced by LT which is the most rapid in vivo or in vitro LT-mediated effect reported to date.Anthrax, the disease caused by Bacillus anthracis, is a worldwide bioterrorism concern. Anthrax toxin, a major virulence factor of this organism, consists of three polypeptides: protective antigen (PA), lethal factor (LF), and edema factor (EF). PA is required for binding and translocation of EF and LF into target cells (5). The injection of lethal toxin (LT is LF plus PA) into animals is sufficient to induce some symptoms of anthrax infection, including pleural effusions indicative of vascular leakage and lethality (3,4,6,10,23,24,28). Early studies suggested that LT kills animals by inducing nonspecific shocklike manifestations (3,36), and recent studies with mice and rats have confirmed an LT-mediated cytokine-independent vascular collapse (6, 28). Humans and primates infected by aerosol exposure to spores present pleural effusions as the most common symptom of disease (8,20,40). Histopathological analyses of human subjects with inhalational anthrax infections as well as studies of nonhuman primates and other animals show hemorrhaging in various organs resulting from destruction of both large and small vessels (1,7,11,15,16,38). However, while observations of pulmonary edema, inflammation, endothelial necrosis, vessel inflammation, increased vascular permeability, and hemorrhage have been associated with bacterial infection, they are not seen in systemic models of mouse and rat LT toxicity (6, 28). Clearly, LT is a single virulence factor in t...

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

Anthrax Lethal Toxin Induces Ketotifen-Sensitive Intradermal Vascular Leakage in Certain Inbred Mice

et al. 2006

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“…The endotoxin syndrome is associated with a release of in¯ammatory mediators including eicosanoids, cytokines, platelet-activating factor (PAF) and nitric oxide (Liao, 1996;Karima et al, 1999). Subcutaneous injection of LPS on the back of mice/rats induces a plasma leakage at the site of injection, which has been used as an in vivo model of in¯ammation (Fujii et al, 1996a, b;Iuvone et al, 1999). This LPS-induced increase in vascular permeability is mediated by TNF-a, IL-1a, histamine, nitric oxide, PAF and prostaglandins in the mouse (Fujii et al, 1996a, b;Wada et al, 2000) and by histamine, nitric oxide and TNF-a in the rat (Iuvone et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Inhibitory effects of cyclic AMP elevating agents on lipopolysaccharide (LPS)‐induced microvascular permeability change in mouse skin

Irie

Fujii

Ishida

et al. 2001

British J Pharmacology

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1 Anti-in¯ammatory e ects of cyclic AMP elevating agents were examined in a mouse model of lipopolysaccharide (LPS)-induced microvascular permeability change. 2 Vascular permeability on the back skin was measured by the local accumulation of Pontamine sky blue (PSB) after subcutaneous injection of LPS (400 mg site 71 ) from Salmonella typhimurium. 3 Dye leakage in the skin was signi®cantly increased 2 h after injection of LPS. This LPS-induced dye leakage was suppressed by phosphodiesterase inhibitors, including pentoxifylline (160 mg kg 71 ), milrinone (5 ± 10 mg kg 71 ), rolipram (0.5 ± 10 mg kg 71 ) and zaprinast (5 ± 10 mg kg 71 ). The dye leakage was also inhibited by b-adrenoceptor agonists, including isoproterenol (0.5 ± 5 mg kg 71 ) and salbutamol (0.05 ± 5 mg kg 71 ), an adenylate cyclase activator, forskolin (5 mg kg 71 ), and a cell permeable cyclic AMP analogue, 8-bromo-cyclic AMP (8-Br-cAMP, 10 mg kg 71 ). 4 LPS caused a transient increase in serum TNF-a level peaking at 1 h after the injection. This increase in serum TNF-a was completely blocked by a pretreatment with pentoxifylline (160 mg kg 71 ), milrinone (5 mg kg 71 ), rolipram (1 mg kg 71 ), zaprinast (10 mg kg 71 ), salbutamol (0.5 mg kg 71 ), forskolin (1 mg kg 71 ) and 8-Br-cAMP (10 mg kg 71 ). 5 LPS caused an increase in serum IL-1a level peaking at 3 h after injection. This increase in serum IL-1a was not signi®cantly suppressed by the cyclic AMP elevating agents. 6 Our study suggests that cyclic AMP elevating agents attenuate LPS-induced microvascular permeability change by suppressing TNF-a up regulation.

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“…as tumor necrosis factor-alpha (TNF-α) and histamine, with the mast cell degranulation [14] . Therefore, many investigators have made much effort to abolish or reduce the LPS-elicited injury.…”

Section: Compound Danshen Injection Improves Endotoxin-induced Microcmentioning

confidence: 99%

Compound Danshen injection improves endotoxin-induced microcirculatory disturbance in rat mesentery

Han

Horie²,

Miura³

et al. 2007

WJG

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stained with Monastral blue B, rolling and adhesion of leukocytes, production of oxygen radical in venular wall, albumin efflux and enhanced mast cell degranulation in vivo , all of which, except for the leukocyte rolling, were attenuated by the treatment with compound Danshen injection. Experiments performed in vitro further revealed that the expression of CD11b/CD18 and the production of oxygen free radical in neutrophils, and the expression of ICAM-1 in HUVECs were increased by exposure to LPS, and they were attenuated by compound Danshen injection. CONCLUSION: These results suggest that compoundDanshen injection is an efficient drug with multi-targeting potential for improving the microcirculatory disturbance. INTRODUCTIONIt is now well-recognized that stimulation with lipopolysaccharide (LPS) leads to a number of responses in microcirculation, such as endothelial cell damage, an increase in rolling, adhesion and emigration of leukocytes in post-capillary venules, enhanced oxygenfree radical production, mast cell degranulation and protein efflux [1][2][3][4][5][6] . Furthermore, it is demonstrated that LPS stimulation evokes an increase in the expression of adhesion molecules, including L-selectin [7] and CD11b/CD18 in leukocytes, E-selectin and intercellular adhesion molecule 1 (ICAM-1) in endothelial cells [7][8][9][10][11][12][13] . In addition, LPS stimulation can cause the release of proinflammatory mediators and vasoactive substances, such Abstract AIM: To investigate the effect of compound Danshen injection on lipopolysaccharide (LPS)-induced rat mesenteric microcirculatory dysfunctions and the underlying possible mechanism by an inverted intravital microscope and high-speed video camera system. METHODS:LPS was continuously infused through the jugular artery of male Wistar rats at the dose of 2 mg/kg per hour. Changes in mesenteric microcirculation, such as diameters of arterioles and venules, velocity of RBCs in venules, leukocyte rolling, adhesion and emigration, free radicals released from post-capillary venules, FITCalbumin leakage and mast cell degranulation, were observed through an inverted intravital microscope assisted with CCD camera and SIT camera. Meanwhile, the expression of adhesion molecules CD11b/CD18 and the production of free radical in neutrophils, and the expression of intercellular adhesion molecule 1 (ICAM-1) in human umbilical vein endothelial cells (HUVECs) were quantified by flow cytometry (FACS) in vitro . RESULTS:The continuous infusion with LPS resulted in a number of responses in microcirculation, including a significant increase in the positive region of venule

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Evidence that mast cell degranulation, histamine and tumour necrosis factor α release occur in LPS‐induced plasma leakage in rat skin

Cited by 40 publications

References 28 publications

Anthrax Lethal Toxin Induces Ketotifen-Sensitive Intradermal Vascular Leakage in Certain Inbred Mice

Anthrax Lethal Toxin Induces Ketotifen-Sensitive Intradermal Vascular Leakage in Certain Inbred Mice

Inhibitory effects of cyclic AMP elevating agents on lipopolysaccharide (LPS)‐induced microvascular permeability change in mouse skin

Compound Danshen injection improves endotoxin-induced microcirculatory disturbance in rat mesentery

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