Leukotriene and Prostanoid Pathway Enzymes in Bronchial Biopsies of Seasonal Allergic Asthmatics

Seymour, Michelle L.; Rak, S.; Åberg, Daniel; Riise, Gert C.; Penrose, John F.; Kanaoka, Yoshihide; Austen, K. Frank; Holgate, Stephen T.; Sampson, Anthony P.

doi:10.1164/ajrccm.164.11.2008137

Cited by 47 publications

(39 citation statements)

References 35 publications

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“…It remains to be identified which specific prostanoids are responsible for the phenomenon of force potentiation. Moreover, prostanoids are released as inflammatory mediators and have been shown to play a role in airway responsiveness (16,28). The results from this study suggest that the mechanisms underlying the adaptive behavior of hyperresponsive ASM include factors involved in pathological conditions such as inflammatory response.…”

Section: Discussionmentioning

confidence: 76%

Length oscillation induces force potentiation in infant guinea pig airway smooth muscle

Wang¹,

Chitano²,

Murphy³

2005

American Journal of Physiology-Lung Cellular and Molecular Phys

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-Deep inspiration counteracts bronchospasm in normal subjects but triggers further bronchoconstriction in hyperresponsive airways. Although the exact mechanisms for this contrary response by normal and hyperresponsive airways are unclear, it has been suggested that the phenomenon is related to changes in force-generating ability of airway smooth muscle after mechanical oscillation. It is known that healthy immature airways of both humans and animals exhibit hyperresponsiveness. We hypothesize that the profile of active force generation after mechanical oscillation changes with maturation and that this change contributes to the expression of airway hyperresponsiveness in juveniles. We examined the effect of an acute sinusoidal length oscillation on the force-generating ability of tracheal smooth muscle from 1 wk, 3 wk, and 2-to 3-mo-old guinea pigs. We found that the length oscillation produced 15-20% initial reduction in active force equally in all age groups. This was followed by a force recovery profile that displayed striking maturation-specific features. Unique to tracheal strips from 1-wk-old animals, active force potentiated beyond the maximal force generated before oscillation. We also found that actin polymerization was required in force recovery and that prostanoids contributed to the maturation-specific force potentiation in immature airway smooth muscle. Our results suggest a potentiated mechanosensitive contractile property of hyperresponsive airway smooth muscle. This can account for further bronchoconstriction triggered by deep inspiration in hyperresponsive airways. actin polymerization; deep inspiration; hyperresponsive airways; ontogenesis; prostanoids AIRWAY HYPERRESPONSIVENESS is characterized by increased sensitivity of the tracheobronchial tree to contractile stimuli as well as an increased capacity for airway narrowing. Altered contractility of airway smooth muscle (ASM) is one of the mechanisms potentially responsible for increased airway sensitivity and maximal response. The involvement of ASM in the pathogenesis of airway hyperresponsiveness has long been controversial. However, both the capacity and velocity of shortening have been shown to be elevated in ASM from hyperresponsive airways (14,17). Increased ASM contractility shown in young animals suggests a central role for ASM also in juvenile airway hyperresponsiveness (8). It becomes, therefore, particularly important to study the mechanisms by which ASM function changes with maturation and whether this has a role in juvenile hyperresponsiveness and childhood asthma.An important feature of altered airway function in asthma is the inability of deep inspiration (DI) to improve airway function (37). DI could even induce bronchoconstriction in asthmatic subjects (2, 19). It has been convincingly shown that DI reverses bronchoconstriction in normal subjects by stretching contracted ASM (22). The protective effect of DI gained considerable research interest in recent years due to reports that showed a DI before the administration of a cont...

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Section: Discussionmentioning

confidence: 76%

Length oscillation induces force potentiation in infant guinea pig airway smooth muscle

Wang¹,

Chitano²,

Murphy³

2005

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Each type of the hypersensitivity mechanism, with its own characteristics and including specific parts, such as particular cell types, individual immunoglobulin classes, specific mediators, chemotactic factors, cytokines, chemokines, CD molecules, adhesion molecules, enzymes, activated cellular and tissue receptors, may lead to a specific clinical manifestation of the lower asthmatic airways [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43]. …”

Section: Introductionmentioning

confidence: 99%

Delayed Asthmatic Response to Bronchial Challenge with Allergen-Mediators, Eicosanoids, Eosinophil and Neutrophil Constituents in the Blood and Urine

Pelikán¹

2011

Respiration

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Background: In patients with allergic bronchial asthma, different immunologic mechanisms may participate and lead to different types of asthmatic response to allergen challenge, such as immediate/early (IAR/EAR), late (LAR) or delayed asthmatic response (DYAR). Objectives: In 55 of 397 asthmatics, DYAR has been recorded (p < 0.001) and confirmed by repeated bronchial challenge with the same allergen (p < 0.001). DYAR began between 26 and 32 h, reached a maximum between 32 and 48 h and resolved within 56 h after the challenge. DYAR was associated with various clinical symptoms and diagnostic parameters having diverged from those recorded during the IARs/EARs and LARs. Methods: In 25 of 55 patients, repeated DYAR has been supplemented with the recording of leukotriene B₄ (LTB₄), LTC₄, LTE₄, prostaglandin D₂ (PGD₂), PGE₂, PGF₂_α, thromboxane B₂, lipoxin A₄, eosinophil cationic protein, eosinophil-derived neurotoxin/eosinophil protein X, eosinophilic peroxidase, myeloperoxidase, histamine and tryptase in peripheral blood, and of LTC₄, thromboxane B₂, eosinophil-derived neurotoxin and 9α,11β-PGF₂ in urine, before and up to 72 h after the bronchial allergen challenge, by means of enzyme-linked immunoassay (ELISA/EIA) or ImmunoCAP. Results: DYAR was accompanied by a significant increase in the plasma concentrations of LTB₄ (p < 0.05) and myeloperoxidase (p < 0.05) at 24, 36 and 48 h after the challenge, whereas the plasma/serum or urine concentrations of the other factors did not demonstrate any significant changes (p > 0.05). Conclusions: These results would indicate an active and prominent involvement of neutrophils, in addition to the previously demonstrated role of the Th1 lymphocytes, in the clinical DYAR.

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“…Eosinophils are inflammatory cells predominantly found in the airways of patients with asthma and therefore possibly contribute to the pathophysiology observed in asthma [1,2,3,4]. The mechanism by which eosinophils accumulate in the airways is a complex process which is mainly regulated by cytokines, chemokines, and adhesion molecules.…”

Section: Introductionmentioning

confidence: 99%

Eosinophils Do Not Enhance the Trans-Basement Membrane Migration of Neutrophils

Kobayashi¹,

Takaku²,

Kikuchi³

et al. 2007

Int Arch Allergy Immunol

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Background: There is increasing evidence that both neutrophilic and eosinophilic inflammation persist in the airways of patients with severe asthma. We have reported a positive relationship between the concentrations of eosinophils and neutrophils in sputum from severe asthmatics, suggesting a possible role of eosinophils in regulating neutrophilic inflammation. The aim of this study was to investigate whether activated eosinophils modify the trans-basement membrane migration (TBM) of neutrophils. Methods: Eosinophils and neutrophils were isolated from peripheral blood drawn from healthy donors. The TBM of neutrophils in response to a variety of chemoattractants was evaluated in the presence or absence of eosinophils by using the chambers with a Matrigel®-coated Transwell® insert. Results: As expected, eotaxin (10 nM) and RANTES (10 nM), but not IL-8 (10 nM), induced the TBM of eosinophils. On the contrary, only IL-8 induced the TBM of neutrophils. When eosinophils were coincubated with neutrophils and stimulated with IL-8, the TBM of eosinophils was significantly augmented. On the other hand, when neutrophils were coincubated with eosinophils and stimulated with eotaxin or RANTES, the TBM of neutrophils was not modified. Conclusions: Neutrophils migrated by IL-8 may lead eosinophils to accumulate in the airways of patients with severe asthma. On the other hand, it is unlikely that eosinophils migrated by chemoattractants such as CC chemokines regulate neutrophilic inflammation.

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Leukotriene and Prostanoid Pathway Enzymes in Bronchial Biopsies of Seasonal Allergic Asthmatics

Cited by 47 publications

References 35 publications

Length oscillation induces force potentiation in infant guinea pig airway smooth muscle

Length oscillation induces force potentiation in infant guinea pig airway smooth muscle

Delayed Asthmatic Response to Bronchial Challenge with Allergen-Mediators, Eicosanoids, Eosinophil and Neutrophil Constituents in the Blood and Urine

Eosinophils Do Not Enhance the Trans-Basement Membrane Migration of Neutrophils

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