A bradykinin-antagonist blocks antigen-induced airway hyperresponsiveness and inflammation in sheep

Solèr, Markus; Sielczak, M. W.; Abraham, William M.

doi:10.1016/0952-0600(90)90003-2

Cited by 53 publications

(31 citation statements)

References 19 publications

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“…Such results are consistent with our previous observations that cationic charge is an important determinant of the ability of these proteins to increase airway responsiveness (7). To (27), inhibition of bradykinin with the selective antagonist NPC 567 inhibited the development of antigen-induced AHR in allergic sheep (28). Thus while the generation of bradykinin is central to the expression of airway responsiveness induced by either allergen (28) (34)(35)(36).…”

Section: Discussionsupporting

confidence: 81%

Human eosinophil-granule major basic protein and synthetic polycations induce airway hyperresponsiveness in vivo dependent on bradykinin generation.

Coyle¹,

Ackerman²,

Burch³

et al. 1995

J. Clin. Invest.

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In the current series of experiments we investigated the role of bradykinin in airway hyperresponsiveness induced by human eosinophil-granule major basic protein (MBP). Bronchoalveolar lavage was performed after intratracheal instillation of MBP or poly-L-lysine in anesthetized, intubated rats, and levels of immunoreactive kinins and kallikrein-like activity were determined. Both MBP and poly-Llysine induced a three-and eightfold increase in levels of kallikrein-like activity and i-kinins, respectively. To determine whether kinin production is required for the development of airway hyperresponsiveness induced by cationic proteins, dose-response curves to methacholine were constructed before and 1 h after intratracheal instillation of either MBP or poly-L-lysine (100 pg). MBP and poly-Llysine induced an increase in airway responsiveness, which was inhibited by pretreatment with a selective BK-2 receptor antagonist, NPC 17713 (250 jug/ml). Our results demonstrate that MBP and poly-L-lysine activate kallikrein and stimulate the generation of i-kinins in vivo, an effect that may be related to the cationic charge of these proteins. Furthermore, the ability of these proteins to increase airway responsiveness appears to be dependent on the generation of i-kinins. (J. CliU. Invest. 1995Invest. .95:1735Invest. -1740

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Section: Discussionsupporting

confidence: 81%

Human eosinophil-granule major basic protein and synthetic polycations induce airway hyperresponsiveness in vivo dependent on bradykinin generation.

Coyle¹,

Ackerman²,

Burch³

et al. 1995

J. Clin. Invest.

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“…The provocation test was discontinued when SRL increased over 400% from the post-saline value or after the highest carbachol concentration had been administered. Bronchial responsiveness was assessed as previously described (36,37) by determining the cumulative carbachol concentration (in breath units [BUI) that increased SRL by 400% over the post-saline value (PC4w) by interpolation from the dose response curve. One BU was defined as one breath of a 1% wt/vol carbachol aerosol solution.…”

Section: In Vitro Studiesmentioning

confidence: 99%

“…Plates were blocked with 1% BSA in PBS for 1 h at room temperature, washed once with RPMI 1640 containing 10% FBS (RPMI/ 10), and adhesion assays with sheep peripheral blood mononuclear leukocytes were performed with inverted centrifugation as described ( 11,32). Blood leukocyte adhesion was quantified by fluorescence as described (33 (36)(37)(38). Pleural pressure was estimated with the esophageal balloon catheter (filled with I ml of air), which was positioned 5-10 cm from the gastroesophageal junction.…”

Section: In Vitro Studiesmentioning

confidence: 99%

Alpha 4-integrins mediate antigen-induced late bronchial responses and prolonged airway hyperresponsiveness in sheep.

Abraham¹,

Sielczak²,

Ahmed³

et al. 1994

J. Clin. Invest.

206

119

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“…Bradykinin has been reported to contribute to the increase in bronchial reactivity that follows allergen challenge in sheep [19]. This effect is not related to changes either in airway smooth muscle or in muscarinic and histamine (H 1 ) receptor density or function, and is probably the consequence of the ability of a selective bradykinin antagonist to reduce pulmonary inflammation [26].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, bradykinin is reported to possess many pharmacological properties pertinent to the pathogenesis of asthma. These include vasodilatation and increased microvascular leakage [12,13], bronchoconstriction [14,15], modulation of mucociliary transport [16,17], activation of C-fibre nociceptive sensory nerve endings [16,18], and induction of nonspecific bronchial hyperresponsiveness in animals [19].…”

mentioning

confidence: 99%

Effect of inhaled bradykinin on indices of airway responsiveness in asthmatic subjects

Polosa¹,

Rajakulasingam²,

Prosperini³

et al. 1994

Eur Respir J

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E Ef ff fe ec ct t o of f i in nh ha al le ed d b br ra ad dy yk ki in ni in n o on n iin nd di ic ce es s o of f a ai ir rw wa ay y r re es sp po on ns si iv ve en ne es ss s i in n a as st th hm ma at ti ic c s su ub bj je ec ct ts s We have, therefore, investigated the effect of inhaled bradykinin on the changes in airway calibre and in airway hyperresponsiveness to histamine, in a double-blind, randomized study of nine asthmatic subjects. Subjects were studied on two study periods, separated by at least 15 days. On the first day of each study period, subjects inhaled either a single dose of bradykinin or methacholine (placebo) with changes in airway calibre being followed as forced expiratory volume in one second (FEV 1 ) and as the maximum expiratory flow rate measured at 70% of the vital capacity below total lung capacity (TLC) from a partial forced expiratory manoeuvre (Vp 30 ) Inhalation of bradykinin caused rapid bronchoconstriction that peaked at 3-5 min. When compared to placebo, no significant difference in histamine responsiveness was seen after bradykinin in terms of changes in PC 20 FEV 1 values. However, when airway hyperresponsiveness was measured as PC 40 Vp 30 , we were able to show a significant increase in airway reactivity after bradykinin at 3 and 7 h, the geometric mean PC 40 Vp 30 histamine value decreasing 3.2 and 1.9 fold, respectively.The results of the present study indicate that bradykinin elicits a transient increase of airway hyperresponsiveness in asthmatic subjects, but this was evident only using a sensitive indicator of the changes in airway reactivity, which suggests an effect at the level of the more peripheral airways. These data suggest that bradykinin may play a role in the pathogenesis of airway hyperresponsiveness in human asthma.

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A bradykinin-antagonist blocks antigen-induced airway hyperresponsiveness and inflammation in sheep

Cited by 53 publications

References 19 publications

Human eosinophil-granule major basic protein and synthetic polycations induce airway hyperresponsiveness in vivo dependent on bradykinin generation.

Human eosinophil-granule major basic protein and synthetic polycations induce airway hyperresponsiveness in vivo dependent on bradykinin generation.

Alpha 4-integrins mediate antigen-induced late bronchial responses and prolonged airway hyperresponsiveness in sheep.

Effect of inhaled bradykinin on indices of airway responsiveness in asthmatic subjects

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