Correlation between Increased Airway Responsiveness and Severity of Pulmonary Edema

Hwang, Young Sil; Lefferts, Peter L.; Snapper, James R.

doi:10.1006/pupt.2000.0266

Cited by 6 publications

(6 citation statements)

References 17 publications

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“…Mice lacking SP-A and infected with Mp had significantly more total protein in BALF than wild type mice (see figure 2G). This finding was particularly interesting since decreases in compliance indicate increased stiffness in the lungs which is often clinically correlated with increased pulmonary edema (41, 42). Taken together these findings are consistent with the significantly lower lung compliance observed in the infected SP-A null Mp mice and assessed prior to methacholine provocations.…”

Section: Discussionmentioning

confidence: 96%

SP-A Preserves Airway Homeostasis During Mycoplasma pneumoniae Infection in Mice

Ledford

Goto

Potts

et al. 2009

The Journal of Immunology

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The lung is constantly challenged during normal breathing by a myriad of environmental irritants and infectious insults. Pulmonary host defense mechanisms maintain homeostasis between inhibition/clearance of pathogens and regulation of inflammatory responses that could injure the airway epithelium. One component of this defense mechanism, surfactant protein-A (SP-A), exerts multifunctional roles in mediating host responses to inflammatory and infectious agents. SP-A has a bacteriostatic effect on Mycoplasma pneumoniae (Mp), which occurs by binding surface disaturated phosphatidylglycerols. SP-A can also bind the Mp membrane protein, MPN372. In this study we investigated the role of SP-A during acute phase pulmonary infection with Mp using mice deficient in SP-A. Biologic responses, inflammation and cellular infiltration, were much greater in Mp infected SP-A−/− mice than wild type mice. Likewise, physiologic responses (airway hyperresponsiveness and lung compliance) to Mp infection were more severely affected in SP-A−/− mice. Both Mp-induced biologic and physiologic changes were attenuated by pharmacologic inhibition of TNF-α. Our findings demonstrate that SP-A is vital to preserving lung homeostasis and host defense to this clinically relevant strain of Mp by curtailing inflammatory cell recruitment and limiting an overzealous TNF-α response.

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Section: Discussionmentioning

confidence: 96%

SP-A Preserves Airway Homeostasis During Mycoplasma pneumoniae Infection in Mice

Ledford

Goto

Potts

et al. 2009

The Journal of Immunology

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“…The inflammatory edema observed after chronic LPS exposure may be a result of an increased capillary blood pressure by vasoconstrictor eicosanoids or an increased permeability of the capillary wall from the release of reactive oxygen species (including NO and peroxynitrite), eicosanoids, or proteolytic enzymes (Brigham and Meyrick, 1986;Barnes et al, 1999). Edematous swelling of the airway wall and increased airway exudate in the lung have been shown to reduce airway caliber and correlate with AHR in sheep (Hwang et al, 2001), and may contribute to the AHR observed in the present chronic LPS model. Edema is also a probable contributor to the prolonged bronchoconstriction seen in this study after chronic LPS exposure.…”

mentioning

confidence: 64%

Goblet Cell Hyperplasia, Airway Function, and Leukocyte Infiltration after Chronic Lipopolysaccharide Exposure in Conscious Guinea Pigs: Effects of Rolipram and Dexamethasone

Toward¹,

Broadley²

2002

J Pharmacol Exp Ther

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The effects of chronic exposures (nine, 48 h apart) of conscious guinea pigs to lipopolysaccharide (LPS) (30 g ⅐ ml Ϫ1 , 1 h) on airway function, airway histology (in particular, goblet cell numbers), and inflammatory cell infiltration of the lungs were examined as a model of chronic inflammatory lung disease, such as chronic obstructive pulmonary disease. The sensitivity of these parameters to treatment with the corticosteroid, dexamethasone, or the phosphodiesterase-4 (PDE4) inhibitor, rolipram, was determined. As the number of LPS exposures increased, there was a progressively persistent bronchoconstriction after each exposure. After nine LPS exposures, there was evidence on histological examination of airway infiltration of, predominantly, neutrophils in perivascular, peribronchial, and alveolar tissues. After chronic LPS exposure, the airway epithelium possessed a marked goblet cell hyperplasia and evidence of inflammatory edema, features contributory to reduced airway caliber. Treatment with dexamethasone (20 mg ⅐ kg Ϫ1 ) or rolipram (1 mg ⅐ kg Ϫ1 ), administered (i.p.) 24 and 0.5 h before exposure and 24 and 47 h after each subsequent exposure, attenuated the inflammatory cell infiltration into the airway, goblet cell hyperplasia, and inflammatory edema. Dexamethasone exacerbated, whereas rolipram reversed, the chronic LPS-induced bronchoconstrictions. This study demonstrates that chronic LPS causes persistent bronchoconstriction, neutrophilic airway inflammation, goblet cell hyperplasia, and edema. These rolipram-sensitive features suggest the potential of PDE4 inhibitors in chronic inflammatory lung diseases.Chronic mucus hypersecretion is an important symptomatic and pathological feature of a heterogeneous group of chronic respiratory diseases that includes chronic bronchitis, chronic obstructive pulmonary disease (COPD), and asthma (Rogers, 1994;Jackson, 2001). Persistent mucus overproduction contributes to reduced airway caliber and the occlusion of small airways (reduced FEV 1 ), productive cough, and labored breathing (Jackson, 2001). Individuals with chronic mucus hypersecretion also suffer from an increased frequency and duration of respiratory infection, causing further exacerbation of their original respiratory pathology (Jackson, 2001).The two major sources of mucus secretion in the respiratory tract are the surface epithelial goblet cells and mucous cells of the submucosal glands. In normal lungs, goblet cells are present in the large bronchi, becoming increasingly sparse toward the bronchioles. The submucosal glands are restricted to the large airways with their density decreasing with airway caliber, such that they are absent in the bronchioles. In chronic respiratory diseases, such as COPD and asthma, submucosal glands increase in size (hypertrophy), and the number of goblet cells is increased (hyperplasia), becoming more dense in the peripheral airways, via a phenotypic conversion of nongoblet epithelial cells (metaplasia) (Rogers, 1994;Jackson, 2001). The increased ratio of goble...

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“…The increase in wet lung weight is likely to arise from oedema (Hwang et al, 2001). An increase in lung oedematous uid may be a result of an increased capillary blood pressure or an increase in permeability of the capillary wall.…”

Section: Discussionmentioning

confidence: 99%

“…However, as ozone and ROS are potent mucus secretagogues, the secretion of mucus from goblet cells and submucosa glands could also increase the lung wet weight and reduce airway calibre, thus causing bronchoconstriction (Barnes et al, 1999;Bousquet et al, 2000). A reduced airway calibre is also a likely cause of the AHR during the LBP, since it parallels the increase in lung wet weight (Hwang et al, 2001), and a reduced geometric airway calibre would potentiate spasmogenic contractility to inhaled histamine (Pare & Hogg, 1989). However, tachykinininduced neuronal hypersensitivity, peroxynitrite, or epithelial damage exposing airway sensory nerves are also likely contributors of the AHR associated with the LBP in this study (Nijkamp & Folkerts, 1995;Spina et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Airway function, oedema, cell infiltration and nitric oxide generation in conscious ozone‐exposed guinea‐pigs: effects of dexamethasone and rolipram

Toward

Broadley

2002

British J Pharmacology

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1 The e ects of ozone inhalation (90 min, 2.15+0.05 p.p.m.) and their modi®cation by dexamethasone (20 mg kg 71 ) or the phosphodiesterase-4 inhibitor, rolipram (1 mg kg 71 ), administered (i.p.) 24 and 0.5 h before and 24 h after ozone exposure were examined in conscious guineapigs. 2 Ozone caused an early-phase bronchoconstriction (EPB) as a fall in speci®c airways conductance (sG aw ) measured by whole body plethysmography, followed at 5 h by a late-phase bronchoconstriction (LPB) and increased respiratory rate. Rolipram did not alter this pro®le but dexamethasone inhibited the EPB. 3 Airway hyperreactivity to inhaled histamine (1 mM, 20 s) occurred at 0.5, 2, 12, 24 and 48 h after ozone inhalation, the 2 h change being abolished by rolipram and dexamethasone. 4 Bronchoalveolar lavage¯uid (BALF) macrophages, eosinophils and neutrophils were signi®cantly (P50.05) elevated at 12, 24 and 48 h after ozone exposure, the 48 h in¯ux being signi®cantly attenuated (P50.05) by rolipram and dexamethasone. 5 BALF nitric oxide (NO) metabolites decreased 0.5 h after ozone exposure by 52%, recovered at 2 h and signi®cantly increased at 12 (101%) and 24 h (127%). The elevated NO was una ected by rolipram or dexamethasone. 6 Lung oedema, measured from wet/dry weight di erences, was signi®cant 12, 24 and 48 h after ozone exposure, the latter being signi®cantly attenuated (P50.05) by rolipram and dexamethasone. 7 Ozone exposure of guinea-pigs produced features common to COPD. Although rolipram and dexamethasone did not a ect the airway function changes, they inhibited the in¯ammation, airway hyperreactivity and oedema.

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Correlation between Increased Airway Responsiveness and Severity of Pulmonary Edema

Cited by 6 publications

References 17 publications

SP-A Preserves Airway Homeostasis During Mycoplasma pneumoniae Infection in Mice

SP-A Preserves Airway Homeostasis During Mycoplasma pneumoniae Infection in Mice

Goblet Cell Hyperplasia, Airway Function, and Leukocyte Infiltration after Chronic Lipopolysaccharide Exposure in Conscious Guinea Pigs: Effects of Rolipram and Dexamethasone

Airway function, oedema, cell infiltration and nitric oxide generation in conscious ozone‐exposed guinea‐pigs: effects of dexamethasone and rolipram

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