Bronchoalveolar Neutrophilia during Late Asthmatic Reactions Induced by Toluene Diisocyanate

Fabbri, Leonardo; Boschetto, Pierà; Zocca, E.; Milani, G. F.; Pivirotto, F; Plebani, Mario; Burlina, Angelo; Licata, Baldassare; Mapp, C. E.

doi:10.1164/ajrccm/136.1.36

Cited by 287 publications

(115 citation statements)

References 5 publications

Supporting

Mentioning

107

Contrasting

Order By: Relevance

“…The SDX model is primarily one of eosinophilic inflammation, although an early transient increase of neutrophils is observed [2]. Thus, this model shows similarities to human asthma which is likewise characterized by an eosinophilic inflammatory response, preceded by neutrophilia in asthmatic reactions [30]. The considerably higher ET-1 production in the SDX model can not be attributed to the degree of inflammation, since the extent of inflammation induced by LPS, as measured by the recruitment of inflammatory cells into BALF and tissue, is more severe.…”

Section: Discussionmentioning

confidence: 80%

Endothelin-1 production is associated with eosinophilic rather than neutrophilic airway inflammation

et al. 2000

View full text Add to dashboard Cite

Endothelin‐1 (ET‐1) is a strong bronchoconstrictor which possesses pro‐inflammatory properties and is claimed to be an important mediator in bronchial asthma. The present study was undertaken to investigate whether ET‐1 synthesis, in an inflammation dominated by neutrophilic granulocytes, is as pronounced as previously demonstrated in an airway inflammation dominated by eosinophils. Moreover, the authors compared the production of ET‐1 and tumour necrosis factor (TNF)‐α in rat lungs following intratracheal instillation of either lipopolysaccharide (LPS) (neutrophilic inflammation) or Sephadex (SDX) (eosinophilic). The lung tissue ET‐1 messenger ribonucleic acid (mRNA) expression was not increased in LPS treated animals whereas a six‐fold increase was measured after 30 min in the SDX group (p<0.05). TNF‐α mRNA signals increased early following LPS instillation, peaking at 2 h, whereas elevated TNF‐α mRNA in the SDX model was observed at 24 h. The ET‐1 concentrations in bronchoalveolar lavage fluid (BALF) rose slightly, but significantly, 3 h after both LPS and SDX exposure. At 24 h no further rise in ET‐1 levels was observed in the LPS model, while a substantial increase in the ET‐1 concentration was measured in the SDX group (p<0.05). The TNF‐α concentrations in BALF rose considerably at 3 h in the LPS group, but was nearly abolished at 24 h. In SDX challenged animals however, an increase in BALF‐TNF‐α did not occur until 24 h postchallenge. In conclusion, intratracheal instillation of lipopolysaccharide, leading to a purely neutrophilic lung inflammation, does not induce synthesis of endothelin‐1. This is in contrast to observations during an eosinophilic airway inflammation, indicating a specific role of endothelin‐1 in lung inflammations dominated by eosinophils. In contrast to in vitro experiments, no evidence for induction of endothelin‐1 synthesis was observed by high levels of tumour necrosis factor‐αin vivo.

show abstract

Section: Discussionmentioning

confidence: 80%

Endothelin-1 production is associated with eosinophilic rather than neutrophilic airway inflammation

et al. 2000

View full text Add to dashboard Cite

show abstract

“…Given that many investigations have shown neutrophils to be a major cellular component in allergen-induced asthma (2,3,9,27,36,42) and that neutrophils are increased in humans with asthma (42), neutrophils may also be an important mediator in the inflammatory response following sensitization and exposure to an allergen. However, similar to our observations with eosinophils, we did not find a consistent relationship between lung neutrophilia and AHR.…”

Section: Discussionmentioning

confidence: 99%

Allergen-induced airway disease is mouse strain dependent

Whitehead

Walker

Berman

et al. 2003

American Journal of Physiology-Lung Cellular and Molecular Phys

165

119

View full text Add to dashboard Cite

We investigated the development of airway hyperreactivity (AHR) and inflammation in the lungs of nine genetically diverse inbred strains of mice [129/SvIm, A/J, BALB/cJ, BTBR+(T)/tf/tf, CAST/Ei, C3H/HeJ, C57BL/6J, DBA/2J, and FVB/NJ] after sensitization and challenge with ovalbumin (OVA). At 24, 48, and 72 h post-OVA exposure, the severity of AHR and eosinophilic inflammation of the mouse strains ranged from relatively unresponsive to responsive. The severity of the airway eosinophilia of some strains did not clearly correlate with the development of AHR. The temporal presence of T helper type 2 cytokines in lung lavage fluid also varied markedly among the strains. The levels of IL-4 and IL-13 were generally increased in the strains with the highest airway eosinophilia at 24 and 72 h postexposure, respectively; the levels of IL-5 were significantly increased in most of the strains with airway inflammation over the 72-h time period. The differences of physiological and biological responses among the inbred mouse strains after OVA sensitization and challenge support the hypothesis that genetic factors contribute, in part, to the development of allergen-induced airway disease.

show abstract

“…3,4,20 In TDI-induced asthma in human subjects, neutrophilia in BAL fluid has been found in association with asthmatic reactions induced by isocyanate challenge. 21 Neutrophils could be an important source of proinflammatory cytokines and proteolytic enzymes. 22,23 Sustained release of these inflammatory products enhances neutrophil-induced inflammation in the airway and subsequent airway hyperreactivity.…”

Section: Discussionmentioning

confidence: 99%

A murine model of toluene diisocyanate–induced asthma can be treated with matrix metalloproteinase inhibitor

Lee¹,

Song²,

Lee³

et al. 2001

Journal of Allergy and Clinical Immunology

View full text Add to dashboard Cite

Background: Toluene diisocyanate (TDI) is a leading cause of occupational asthma. TDI-induced asthma is an inflammatory disease of the airways that is associated with airway remodeling. However, there are little data available on the role of matrix metalloproteinases (MMPs) in TDI-induced asthma. Objective: We evaluated whether MMP-9 participates in the airway inflammation in TDI-induced asthma. An additional aim of the present study was to determine whether MMP inhibitors could be effective therapeutic agents for TDIinduced asthma. Methods: We developed a murine model of TDI-induced asthma to examine the involvement of MMPs by performing 2 sensitizations with 3% TDI and 1 challenge with 1% TDI using ultrasonic nebulization. Toluene diisocyanate (TDI), a low-molecular-weight compound widely used in the production of polyurethane foams, automobile paints, varnishes, and related products, is a leading cause of occupational asthma. 1,2 TDIinduced asthma is characterized by hyperresponsiveness and inflammation of the airways. 2,3 This inflammation is associated with infiltration of lymphocytes, eosinophils, and neutrophils into the bronchial lumen. 3,4 Airway remodeling, which often occurs in the bronchial tree, probably arises as a consequence of inflammatory processes.The extracellular matrix is a dynamic structure, and its homeostasis depends on an equilibrium between synthesis and degradation of extracellular matrix components. A balance between the expression of proteases and antiproteases, particularly the matrix metalloproteinases (MMPs) and their inhibitors, maintains this homeostasis under normal conditions. The expression of these same proteases and antiproteases is critical in tissue repair and remodeling in some pulmonary inflammatory diseases. [5][6][7][8] In allergic asthma, the mechanisms of remodeling of the bronchial tree caused by extracellular matrix deposition are well characterized. Of the MMP family, MMP-9 is the major proteinase that induces bronchial remodeling in asthma. 9,10 In addition, MMP-9 induces the migration of eosinophils and neutrophils across basement membranes. 11,12 Recently, MMPs were reported to play a crucial role in the infiltration of ovalbumin-induced airway inflammatory cells and the induction of airway hyperresponsiveness in a murine model of asthma. 13 However, there are little data available on the role of MMPs in TDIinduced asthma.In the present study we developed a murine model of TDI-induced asthma to examine the involvement of

show abstract

Bronchoalveolar Neutrophilia during Late Asthmatic Reactions Induced by Toluene Diisocyanate

Cited by 287 publications

References 5 publications

Endothelin-1 production is associated with eosinophilic rather than neutrophilic airway inflammation

Endothelin-1 production is associated with eosinophilic rather than neutrophilic airway inflammation

Allergen-induced airway disease is mouse strain dependent

A murine model of toluene diisocyanate–induced asthma can be treated with matrix metalloproteinase inhibitor

Contact Info

Product

Resources

About