Role of leukotrienes in exercise-induced bronchoconstriction

Hallstrand, Teal S.; Henderson, William R.

doi:10.1007/s11882-009-0003-8

Cited by 47 publications

(38 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The rate-limiting step in eicosanoid biosynthesis is the release of unesterified arachidonic acid (AA) from the sn-2 position of membrane phospholipids by phospholipase A 2 (PLA 2 ) (9). Recent work has uncovered 10 mammalian secreted PLA 2 s (sPLA 2 s) that may coordinate eicosanoid synthesis with the well-described cytosolic PLA 2 -a (i.e., cPLA 2 a) (10-12).…”

mentioning

confidence: 99%

Regulation and Function of Epithelial Secreted Phospholipase A₂ Group X in Asthma

Hallstrand

Lü

Altemeier

et al. 2013

Am J Respir Crit Care Med

Self Cite

View full text Add to dashboard Cite

Rationale: Indirect airway hyperresponsiveness (AHR) is a fundamental feature of asthma that is manifest as exercise-induced bronchoconstriction (EIB). Secreted phospholipase A 2 group X (sPLA 2 -X) plays a key role in regulating eicosanoid formation and the development of inflammation and AHR in murine models. Objectives: We sought to examine sPLA 2 -X in the airway epithelium and airway wall of patients with asthma, the relationship to AHR in humans, and the regulation and function of sPLA 2 -X within the epithelium. Methods: We precisely phenotyped 34 patients with asthma (19 with and 15 without EIB) and 10 normal control subjects to examine in vivo differences in epithelial gene expression, quantitative morphometry of endobronchial biopsies, and levels of secreted protein. The regulation of sPLA 2 -X gene (PLA2G10) expression was examined in primary airway epithelial cell cultures. The function of epithelial sPLA 2 -X in eicosanoid formation was examined using PLA 2 inhibitors and murine tracheal epithelial cells with Pla2g10 deletion. Measurements and Main Results: We found that sPLA 2 -X protein is increased in the airways of patients with asthma and that epithelial-derived sPLA 2 -X may be increased in association with indirect AHR. The expression of sPLA 2 -X increases during in vitro epithelial differentiation; is regulated by inflammatory signals including tumor necrosis factor, IL-13, and IL-17; and is both secreted from the epithelium and directly participates in the release of arachidonic acid by epithelial cells. Conclusions: These data reveal a relationship between epithelialderived sPLA 2 -X and indirect AHR in asthma and that sPLA 2 -X serves as an epithelial regulator of inflammatory eicosanoid formation. Therapies targeting epithelial sPLA 2 -X may be useful in asthma.Keywords: airway hyperresponsiveness; asthma; eicosanoid; epithelial cell; secretory phospholipase A 2Indirect airway hyperresponsiveness (AHR) refers to the propensity to develop airway narrowing in response to stimuli such as exercise, osmotic challenge, or adenosine that cause airflow obstruction via inflammatory or neuronal cells that release mediators (1). Exercise-induced bronchoconstriction (EIB) is a prototypical feature of indirect AHR in asthma that occurs in about 30 to 50% of subjects with asthma in cross-sectional studies (2, 3). Prior studies have identified epithelial shedding into the airway lumen and increased production of inflammatory eicosanoids such as leukotrienes in the airways of patients with EIB (4-8). The basis for the dysregulation of eicosanoids in asthma is incompletely understood. The rate-limiting step in eicosanoid biosynthesis is the release of unesterified arachidonic acid (AA) from the sn-2 position of membrane phospholipids by phospholipase A 2 (PLA 2 ) (9). Recent work has uncovered 10 mammalian secreted PLA 2 s (sPLA 2 s) that may coordinate eicosanoid synthesis with the well-described cytosolic PLA 2 -a (i.e., cPLA 2 a) (10-12). sPLA 2 s have several other inflammatory functions, including ...

show abstract

mentioning

confidence: 99%

Regulation and Function of Epithelial Secreted Phospholipase A₂ Group X in Asthma

Hallstrand

Lü

Altemeier

et al. 2013

Am J Respir Crit Care Med

Self Cite

View full text Add to dashboard Cite

show abstract

“…Evidence suggests that antileukotriene drugs may be particularly effective in exercise -induced bronchoconstriction and aspirin -intolerant asthma. 22 Anti -immunoglobulin E Omalizumab is a humanized anti -immunoglobulin E (IgE) monoclonal antibody. A systematic review of placebo -controlled trials of omalizumab in moderate or severe allergic asthma showed that it reduced exacerbation frequency and facilitated corticosteroid withdrawal.…”

Section: Non -Th2 Inflammation Current Therapies Antifungalmentioning

confidence: 99%

Severe asthma: novel advances in the pathogenesis and therapy

Hartley¹,

Berair²,

Brightling³

2014

Polish Archives of Internal Medicine

View full text Add to dashboard Cite

Asthma affects an estimated 300 million people worldwide and is severe in approximately 10% of sufferers. Asthma, especially severe asthma, is a heterogeneous disease that results from complex host-environment interactions. This review article outlines recent advances in both the understanding of pathogenesis and novel therapies. The pathogenesis of severe asthma can be broadly thought of in four domains: T H 2 inflammation, non -T H 2 inflammation, airway remodeling, and airway smooth muscle dysfunction. They can develop independently or partly as a consequence of each other. Interactions between these domains, their causation, and consequent impact upon disordered airway physiology and clinical expression are poorly understood. Recent advances in specific T H 2-and non -T H 2 -targeted therapy, bronchial thermoplasty targeting airway remodeling and advances in therapies for airway smooth muscle dysfunction present new opportunities for treatment and inform our understanding of asthma pathogenesis. As our understanding of the pathogenesis increases, the need for individualized investigation, treatment, and management of asthma becomes more apparent.

show abstract

“…The rate-limiting step in eicosanoid biosynthesis is the release of unesterified arachidonic acid (AA) from the sn-2 position of membrane phospholipids by PLA 2 s [21]. Some sPLA 2 s find importance in the development of asthma through the generation of arachidonic acid (AA).…”

Section: Advances In Vascular Medicinementioning

confidence: 99%

Diverse Functions of Secretory Phospholipases A₂

Shridas

Webb

2014

Advances in Vascular Medicine

View full text Add to dashboard Cite

Phospholipase A 2 enzymes (PLA 2 s) catalyze the hydrolysis of glycerophospholipids at their sn-2 position releasing free fatty acids and lysophospholipids. Mammalian PLA 2 s are classified into several categories of which important groups include secreted PLA 2 s (sPLA 2 s) and cytosolic PLA 2 s (cPLA 2 s) that are calcium-dependent for their catalytic activity and calcium-independent cytosolic PLA 2 s (iPLA 2 s). Platelet-activating factor acetylhydrolases (PAF-AHs), lysosomal PLA 2 s, and adipose-specific PLA 2 also belong to the class of PLA 2 s. Generally, cPLA 2 enzymes are believed to play a major role in the metabolism of arachidonic acid, the iPLA 2 family to membrane homeostasis and energy metabolism, and the sPLA 2 family to various biological processes. The focus of this review is on recent research developments in the sPLA 2 field. sPLA 2 s are secreted enzymes with low molecular weight (with the exception of GIII sPLA 2 ), Ca 2+ -requiring enzymes with a His-Asp catalytic dyad. Ten enzymatically active sPLA 2 s and one devoid of enzymatic activity have been identified in mammals. Some of these sPLA 2 s are potent in arachidonic acid release from cellular phospholipids for the biosynthesis of eicosanoids, especially during inflammation. Individual sPLA 2 enzymes exhibit unique tissue and cellular localizations and specific enzymatic properties, suggesting their distinct biological roles. Recent studies indicate that sPLA 2 s are involved in diverse pathophysiological functions and for most part act nonredundantly.

show abstract

Role of leukotrienes in exercise-induced bronchoconstriction

Cited by 47 publications

References 49 publications

Regulation and Function of Epithelial Secreted Phospholipase A₂ Group X in Asthma

Regulation and Function of Epithelial Secreted Phospholipase A₂ Group X in Asthma

Severe asthma: novel advances in the pathogenesis and therapy

Diverse Functions of Secretory Phospholipases A₂

Contact Info

Product

Resources

About

Role of leukotrienes in exercise-induced bronchoconstriction

Cited by 47 publications

References 49 publications

Regulation and Function of Epithelial Secreted Phospholipase A2 Group X in Asthma

Regulation and Function of Epithelial Secreted Phospholipase A2 Group X in Asthma

Severe asthma: novel advances in the pathogenesis and therapy

Diverse Functions of Secretory Phospholipases A2

Contact Info

Product

Resources

About

Regulation and Function of Epithelial Secreted Phospholipase A₂ Group X in Asthma

Regulation and Function of Epithelial Secreted Phospholipase A₂ Group X in Asthma

Diverse Functions of Secretory Phospholipases A₂