Role of bradykinin B2 receptors and mast cells in the bradykinin-induced skin response in the rat

Morishita, Masashi; Sakamoto, Tatsuo; Ito, Komei; Torii, Shinpei

doi:10.1016/0014-2999(95)00793-8

Cited by 4 publications

(3 citation statements)

References 26 publications

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“…Alternatively, ketotifen also functions as a potent histamine H1 receptor antagonist (14) and therefore could manifest its effects by interfering with histamine released from other sources. Additionally, ketotifen may play an inhibitory role against responses to other vascular mediators, such as bradykinin (31) as well as other rapidly released vasomodulators originating from the endothelium. However, it is clear that this very rapid LTmediated event involves some form of membrane destabilization or transcription-translation-independent mediator, be- cause the time in which it occurs does not allow for protein synthesis events which would lead to the production of proteins responsible for the leakage.…”

Section: Discussionmentioning

confidence: 99%

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: Discussionmentioning

confidence: 99%

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

et al. 2006

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“…This effect is dissociated from its anti‐histaminic effect (Martin & Baggiolini, 1981) and therefore ketotifen has been extensively used to protect mast cells from degranulation. Our results are in agreement with previous studies showing a protective effect of ketotifen on mast cells in bradykinin‐induced plasma leakage in rat skin (Moroshita et al ., 1996) and in LPS‐induced rat colon permeability (Brown et al ., 1998).…”

Section: Discussionmentioning

confidence: 99%

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

Iuvone

Bossche

D’Acquisto

et al. 1999

British J Pharmacology

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1 In the present study we investigated the role of mast cells during in¯ammation in rat skin. As the release of several pro-in¯ammatory mediators, such as histamine and tumour necrosis factor a (TNFa), occurs following mast cell activation we studied whether mast cell degranulation and the release of both histamine (H) and TNFa occurred in a model of lipopolysaccharide (LPS)-induced plasma leakage in rat skin. 2 Plasma leakage in the rat skin was measured over a period of 2 h as the local accumulation of intravenous injection of 125 I-human serum albumin ( 125 I-HSA) in response to intradermal injection of LPS. LPS (10 mg site 71 ) produced an increase of plasma leakage (50.1+2.3 ml site 71 ) as compared to saline (9.0+3.2 ml site 71 ). Histological analysis of rat tissue showed that LPS induced a remarkable mast cell degranulation (59.8+2.1%) as compared to saline (13.5+2.2%). 3 Ketotifen (10 79 ± 10 77 mol site 71 ), a well-known mast cell-membrane stabilizer, produced a doserelated inhibition of LPS-induced plasma leakage by 36+3.5%, 47+4.0%, 60+3.3% respectively. In addition, ketotifen (10 77 mol site 71 ) inhibited mast cell degranulation by 59.2+2.7%. 4 Chlorpheniramine maleate (CPM) (10 79 ± 10 77 mol site 71 ), an H 1 histamine receptor antagonist only partially inhibited LPS-induced plasma leakage in rat skin (38+1.1% at the highest dose). Furthermore, CPM (10 77 mol site 71 ) did not prevent mast cell degranulation. 5 A polyclonal antibody against TNFa (1 : 500, 1 : 100, 1 : 50 v v 71 dilution), locally injected, decreased LPS-induced plasma leakage in the skin by 15+2.0%, 24+2.1% and 50+3.0% respectively. 6 Taken together these results suggest that LPS-induced plasma leakage in rat skin is mediated, at least in part, by mast cell degranulation and by the release of histamine and TNFa from these cells.

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“…It has been shown that bradykinin in rat skin stimulates the mast cells to release histamines (24) and that the activity of plasma kallikrein is inhibited by soybean trypsin inhibitor (Kunitz) (16). Taking these facts into consideration, we hypothesize that our protease stimulates the bradykinin-releasing pathway in rat skin by activating the plasma kallikrein.…”

Section: Discussionmentioning

confidence: 99%

Physicochemical and Biological Properties of an Extracellular Serine Protease of Aeromonas sobria

Yokoyama

Fujii

Noguchi

et al. 2002

Microbiology and Immunology

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Previously, we cloned a protease gene of Aeromonas sobria, determined its nucleotide sequence and established a method of purifying its product. In this study, we examined the properties of the purified protease. The protease was temperature‐labile and had an optimal pH of 7.5. Metallo‐protease inhibitors and a cysteine protease inhibitor did not block the proteolytic activity of the enzyme. The treatment with reagents to modify sulfhydryl group did not reduce the activity. But, serine protease inhibitors did, showing that it was a serine protease. Subsequently, we examined the ability of the protease to enhance vascular permeability in dorsal skin. The protease showed activity and the reaction was inhibited by a simultaneously injected antihistaminic agent. Histopathological examination showed that mast cells appeared around the site where the protease was injected. These findings show that the vascular permeability‐enhancing effect of the protease is due to histamine released at the site. Furthermore, we found that a soybean trypsin inhibitor (Kunitz) did not block the proteolytic action of the protease in vitro, but inhibited its vascular permeability‐enhancing activity in skin. This suggests that a trypsin‐like protease from skin mediates the activity of the protease to enhance its vascular permeability.

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Role of bradykinin B2 receptors and mast cells in the bradykinin-induced skin response in the rat

Cited by 4 publications

References 26 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

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

Physicochemical and Biological Properties of an Extracellular Serine Protease of Aeromonas sobria

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