Allergen-induced late-phase airways obstruction in the pig: mediator release and eosinophil recruitment

Fornhem, C.; Kumlin, Maria; Jm, Lundberg; Alving, Kjell

doi:10.1183/09031936.95.08071100

Cited by 37 publications

(37 citation statements)

References 38 publications

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“…The changes in Raw, CL,dyn and BVC that were observed in the present study as a result of antigen challenge are in agreement with earlier studies in the pig [15,17]. Moreover, pig anatomy has been found to be suitable for experimental investigations into bronchial circulation [18].…”

Section: Discussionsupporting

confidence: 93%

Nitric oxide synthase inhibition augments acute allergic reactions in the pig airways in vivo

Middelveld¹,

Zetterquist²,

Bergman³

et al. 2000

European Respiratory Journal

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The aim of this study was to examine the effects of nitric oxide synthase inhibition on antigen-and histamine-induced acute airway reactions, in order to clarify the possible modulating role of NO.Twelve specific-pathogen-free pigs (sensitized with Ascaris suum antigen) were challenged with an antigen aerosol during mechanical ventilation and anaesthesia. Six pigs were pretreated with), a NO synthase inhibitor, 30 min before challenge. In separate experiments, seven sensitized pigs received histamine (5 mg) aerosols before and after L-NA treatment.It was found that pretreatment with L-NA resulted in an enhanced airways resistance response to antigen (areas under the curve 0±90 min were (meanSEM) 1,119160 versus 55556 (cmH 2 O . L -1 . s -1 . min for controls, p<0.05 (Mann-Whitney Utest), whereas this response to histamine was not affected by L-NA. Moreover, L-NA pretreatment significantly enhanced total protein (1.850.43 versus 0.310.06 g . L -1 , p<0.01) and histamine levels (42.816.0 versus 2.60.8 nM, p<0.05) in bronchoalveolar lavage fluid 45 min after antigen challenge.In conclusion, this study showed that N G -nitro-L-arginine enhanced reactions occurring during the acute allergic reaction in pigs in vivo. This indicates a protective role of nitric oxide, which might occur through downregulation of histamine release from mast cells rather than a direct bronchodilating effect of nitric oxide. Eur Respir J 2000; 16: 836±844.

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Section: Discussionsupporting

confidence: 93%

Nitric oxide synthase inhibition augments acute allergic reactions in the pig airways in vivo

Middelveld¹,

Zetterquist²,

Bergman³

et al. 2000

European Respiratory Journal

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“…They also have mild airway inflammation and ASM hypertrophy or hyperplasia (32). Studies in other laboratories have shown the presence of late pulmonary reactions in sensitized pigs, with suppression of endogenous cortisol (12). In our pig model, the effects of sensitization on lung physiology in vivo are similar to those of several other animal models, including guinea pig (11,16), rat (3), and rabbit (22).…”

Section: Discussionsupporting

confidence: 66%

Decreased airway narrowing and smooth muscle contraction in hyperresponsive pigs

Turner

Noble

Lucas

et al. 2002

Journal of Applied Physiology

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Increased smooth muscle contractility or reduced smooth muscle mechanical loads could account for the excessive airway narrowing and hyperresponsiveness seen in asthma. These mechanisms were investigated by using an allergen-induced porcine model of airway hyperresponsiveness. Airway narrowing to electric field stimulation was measured in isolated bronchial segments, over a range of transmural pressures (0-20 cmH 2O). Contractile responses to ACh were measured in bronchial segments and in isolated tracheal smooth muscle strips isolated from control and test (ovalbumin sensitized and challenged) pigs. Test airways narrowed less than controls (P Ͻ 0.0001). Test pigs showed reduced contractility to ACh, both in isolated bronchi (P Ͻ 0.01) and smooth muscle strips (P Ͻ 0.01). Thus isolated airways from pigs exhibiting airway hyperresponsiveness in vivo are hyporesponsive in vitro. The decreased narrowing in bronchi from hyperresponsive pigs may be related to decreased smooth muscle contractility. These data suggest that mechanisms external to the airway wall may be important to the hyperresponsive nature of sensitized lungs. bronchial hyperreactivity; respiratory mechanics; bronchoconstriction ASTHMATIC AIRWAYS ARE CHARACTERIZED by inflammation and airway hyperresponsiveness (AHR). AHR in vivo in asthmatic patients suggests that narrowing to provocative stimuli is increased. The mechanisms responsible for airway narrowing are thought to involve either altered responses within the airway wall [e.g., airway smooth muscle (ASM) and wall loads] or alterations in factors external to the airway wall (e.g., parenchymal forces). Over recent years, a number of animal models have been developed to examine the role of the airway and the lung in AHR. However, many aspects of airway physiology in asthma remain unclear, for example, the extent of narrowing in airways from asthmatic patients compared with controls and mechanisms by which airway narrowing might be altered in asthma.Smooth muscle contraction is a major determinant of airway diameter; therefore, AHR of asthma may be due to altered contractile behavior of ASM. However, the literature contains conflicting results, with only some studies indicating that ASM contraction is increased in animal models (11,16,30). Other studies provide clear evidence for a decrease in ASM contraction in sensitized animals (29). Responses of smooth muscle isolated from asthmatic patients show similar inconsistency (13, 28). Furthermore, attempts to show a relationship between the contractile properties of ASM and bronchial responsiveness in vivo have been unsuccessful (1,27,33). Despite extensive literature, the importance of ASM to hyperresponsiveness is still unclear, and it is not known whether ASM contraction in asthma is increased or not.The effect of load on ASM shortening is well established (15, 31). Alterations to the ASM load may affect airway narrowing and could be responsible for the exaggerated airway narrowing and AHR seen in asthma. Such alterations include structural changes ...

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“…In addition, pigs are outbred, similar to humans, perhaps better mimicking the effect of environmental influences than do inbred mice. The clinical signs of allergy in pigs are similar to those in humans, and several studies have been reported (11,15,16,32,33,35,41).…”

supporting

confidence: 49%

Effect of Heat-Killed Escherichia coli, Lipopolysaccharide, and Muramyl Dipeptide Treatments on the Immune Response Phenotype and Allergy in Neonatal Pigs Sensitized to the Egg White Protein Ovomucoid

Schmied

Rupa

Garvie

et al. 2012

Clin Vaccine Immunol

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Predisposition to food allergies may reflect a type 2 immune response (IR) bias in neonates due to the intrauterine environment required to maintain pregnancy. The hygiene hypothesis states that lack of early environmental stimulus leading to inappropriate development and bias in IR may also contribute. Here, the ability of heat-killed Escherichia coli, lipopolysaccharide (LPS), or muramyl dipeptide (MDP) to alter IR bias and subsequent allergic response in neonatal pigs was investigated. Three groups of three litters of pigs (12 pigs/litter) were given intramuscular injections of E. coli, LPS, MDP, or phosphate-buffered saline (PBS) (control) and subsequently sensitized to the egg white allergen ovomucoid using an established protocol. To evaluate change in IR bias, immunoglobulin isotype-associated antibody activity (AbA), concentrations of type 1 and 2 and proinflammatory cytokines released from mitogen-stimulated blood mononuclear cells, and the percentage of T-regulatory cells (T-regs) in blood were measured. Clinical signs of allergy were assessed after oral challenge with egg white. The greatest effect on IR bias was observed in MDP-treated pigs, which had a type 2-biased phenotype by isotype-specific AbA, cytokine production, and a low proportion of T-regs. LPS-treated pigs had decreased type 1-and type 2-associated AbA. E. coli-treated pigs displayed increased response to Ovm as AbA and had more balanced cytokine profiles, as well as the highest proportion of T-regs. Accordingly, pigs treated with MDP were more susceptible to allergy than PBS controls, while pigs treated with LPS were less susceptible. Treatment with E. coli did not significantly alter the frequency of clinical signs.

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Allergen-induced late-phase airways obstruction in the pig: mediator release and eosinophil recruitment

Cited by 37 publications

References 38 publications

Nitric oxide synthase inhibition augments acute allergic reactions in the pig airways in vivo

Nitric oxide synthase inhibition augments acute allergic reactions in the pig airways in vivo

Decreased airway narrowing and smooth muscle contraction in hyperresponsive pigs

Effect of Heat-Killed Escherichia coli, Lipopolysaccharide, and Muramyl Dipeptide Treatments on the Immune Response Phenotype and Allergy in Neonatal Pigs Sensitized to the Egg White Protein Ovomucoid

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