Induction of bronchial hypersensitivity: evidence for a role for prostaglandins.

Walters, EH; Parrish, R W; Bevan, C; Smith, A P

doi:10.1136/thx.36.8.571

Cited by 54 publications

(18 citation statements)

References 17 publications

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“…In contrast, PGHS-derived eicosanoids have been reported to have both detrimental and beneficial effects in the airway, thus their role in the development of allergic lung disease is more complex. For example, PGD 2 , PGF 2α , and TxA 2 cause bronchoconstriction and are thought to be important in the development of airway hyperresponsiveness in animals and humans (8,9,(32)(33)(34). On the other hand, PGE 2 is a bronchodilator, blocks the early and late asthmatic responses to allergen challenge, and prevents the bronchoconstriction that accompanies nonsteroidal anti-inflammatory agent ingestion in aspirinsensitive asthmatics (9,13,(15)(16)(17).…”

Section: Discussionmentioning

confidence: 99%

Allergic lung responses are increased in prostaglandin H synthase–deficient mice

Gavett¹,

Madison²,

Chulada³

et al. 1999

J. Clin. Invest.

187

164

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To investigate the function of prostaglandin H synthase-1 and synthase-2 (PGHS-1 and PGHS-2) in the normal lung and in allergic lung responses, we examined allergen-induced pulmonary inflammation and airway hyperresponsiveness in wild-type mice and in PGHS-1 -/-and PGHS-2 -/-mice. Among nonimmunized saline-exposed groups, we found no significant differences in lung function or histopathology, although PGE 2 was dramatically reduced in bronchoalveolar lavage (BAL) fluid from PGHS-1 -/-mice, relative to wild-type or PGHS-2 -/-mice. After ovalbumin sensitization and challenge, lung inflammatory indices (BAL cells, proteins, IgE, lung histopathology) were significantly greater in PGHS-1 -/-mice compared with PGHS-2 -/-mice, and both were far greater than in wild-type mice, as illustrated by the ratio of eosinophils in BAL fluid (8:5:1, respectively). Both allergic PGHS-1 -/-and PGHS-2 -/-mice exhibited decreased baseline respiratory system compliance, whereas only allergic PGHS-1 -/-mice showed increased baseline resistance and responsiveness to methacholine. Ovalbumin exposure caused a modest increase in lung PGHS-2 protein and a corresponding increase in BAL fluid PGE 2 in wild-type mice. We conclude that (a) PGHS-1 is the predominant enzyme that biosynthesizes PGE 2 in the normal mouse lung; (b) PGHS-1 and PGHS-2 products limit allergic lung inflammation and IgE secretion and promote normal lung function; and (c) airway inflammation can be dissociated from the development of airway hyperresponsiveness in PGHS-2 -/-mice.

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Section: Discussionmentioning

confidence: 99%

Allergic lung responses are increased in prostaglandin H synthase–deficient mice

Gavett¹,

Madison²,

Chulada³

et al. 1999

J. Clin. Invest.

187

164

View full text Add to dashboard Cite

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“…Four of this group proved to have lung cancer, always on the side opposite to the one that was lavaged. The study followed internationally agreed guidelines27 and all subjects fulfilled the following criteria: (1) age 16-75 years, with an FEV, over 60% of the predicted value; (2) no oral corticosteroids for at least the previous three months; (3) no evidence of a chest or upper respiratory tract infection within eight weeks.…”

Section: Subjectsmentioning

confidence: 99%

Number and activity of inflammatory cells in bronchoalveolar lavage fluid in asthma and their relation to airway responsiveness.

Kelly

Ward

Stenton

et al. 1988

Thorax

Self Cite

182

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Bronchial responsiveness to inhaled methacholine was measured four to six days before fibreoptic bronchoscopy in 22 asthmatic patients (10 smokers) and 20 control subjects (12 smokers).The asthmatic patients had a baseline FEV, greater than 60% predicted and a PD20FEV, (provocative dose of methacholine causing a 20% fall in FEV,) of 0 006-3-7 mg. The 20 control subjects had normal pulmonary function and a PD20FEV, above the maximum cumulative dose of methacholine of 6-4 mg. Bronchoalveolar lavage of a middle lobe segment (lingula in four subjects) was performed with three sequential 60 ml aliquots of sterile saline. Cellular metabolic activity was stimulated with latex in aliquots of resuspended cells, and measured by means of luminol enhanced chemiluminescence to assess neutrophil activity and lucigenin enhanced chemiluminescence to assess macrophage activity. Mean absolute total cell counts were similar in the asthmatic and control groups but there were differences in differential cell counts, with a significant increase in eosinophil (p < 0 05) and lymphocyte (p < 0 05) counts in asthma. PD20FEV, was negatively correlated with percentage neutrophil counts (p < 0005). Luminol enhanced chemiluminescence/1000 neutrophils was increased about twofold in asthmatic subjects (p < 0 001), but was not correlated with PD20FEV1. Lucigenin enhanced chemiluminescence/1000 macrophages was increased nearly fourfold in asthmatic patients (p < 0-001) and showed a negative correlation with PD20FEV, (p < 0-01). The macrophage count was increased twofold in current smokers in both groups, but other cell numbers were not altered significantly. Smoking did not affect cellular metabolic activity in either group. This study supports the idea that an inflammatory process is present in the airways of those with asthma, and suggests a relation between bronchial responsiveness and both neutrophil numbers and macrophage activity.

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“…Several other investigations have suggested that inflammation is responsible for a change in the airways responsiveness, possibly due to the superficial location of irritant subepithelial receptors, and the associated bronchial inflammatory response that might occur after heavy irritant exposure. 46,47 Presently, the OSHA PEL for chlorine is 1 ppm as a ceiling limit. The NIOSH REL and ACGIH TLV for chlorine are 0.5 ppm as a TWA; however, the REL is based on a 10-hour workday while the TLV is based on an 8-hour workday.…”

Section: Chlorine and Pulmonary Toxicitymentioning

confidence: 99%

HETA 91-0230-2543, International Association of Fire Fighters (IAFF), Henderson, Nevada.

1995

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Induction of bronchial hypersensitivity: evidence for a role for prostaglandins.

Cited by 54 publications

References 17 publications

Allergic lung responses are increased in prostaglandin H synthase–deficient mice

Allergic lung responses are increased in prostaglandin H synthase–deficient mice

Number and activity of inflammatory cells in bronchoalveolar lavage fluid in asthma and their relation to airway responsiveness.

HETA 91-0230-2543, International Association of Fire Fighters (IAFF), Henderson, Nevada.

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