Evaluation of leukotriene biosynthetic capacity in lung tissues from horses with recurrent airway obstruction

Lindberg, Annelie; Näsman-Glaser, Barbro; Lindgren, Jan; Robinson, N. E.

doi:10.2460/ajvr.2002.63.794

Cited by 6 publications

(5 citation statements)

References 34 publications

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“…Although LT 4 H has long been known to generate leukotriene B 4 (LTB 4 ), it has also been recently shown to possess aminopeptidase activity for PGPs (38). While the presence of LT 4 H in BALF of human asthmatic patients and horses with heaves has not, to our knowledge, been investigated to date, equine and human lungs have endogenous LT 4 H activity (8,21), and we have recently reported its increased expression in the lung tissue of diseased horses compared with controls (18). The lack of differences between groups in PGP or N-␣-PGP may also have resulted by the difficulty to correct for possible dilution effects of epithelial lining fluids when studying BALFs (43).…”

Section: Discussionmentioning

confidence: 98%

Airway collagen and elastic fiber content correlates with lung function in equine heaves

Setlakwe

Lemos

Lavoie-Lamoureux

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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The consequences on lung function and inflammation of alterations in the extracellular matrix affecting the peripheral airway wall in asthma are largely unknown. We hypothesized that remodeling of collagen and elastic fibers in the peripheral airway wall leads to airway obstruction and contributes to neutrophilic airway inflammation. Animals used were six heaves-affected horses and five controls. Large peripheral lung biopsies were obtained from horses with heaves in clinical remission (Baseline) and during disease exacerbation and from age-matched controls. The area of collagen and elastic fiber content in the lamina propria was measured by histological staining techniques and corrected for airway size. Collagen type 1 and type 3 content was further assessed from additional horses after postmortem lung samples by immunohistochemistry. The collagen breakdown products proline-glycine-proline (PGP) and N-acetylated-PGP (N-α-PGP) were also measured in bronchoalveolar lavage fluids (BALF) by mass spectrometry. Compared with controls, heaves-affected horses had an increase in collagen (P = 0.05) and elastic fiber contents (P = 0.04) at baseline. Collagen types 1 and 3 content was also significantly increased in diseased horses (P = 0.015) when both collagen types were combined. No further change in collagen content was observed after a 30-day antigenic challenge. Airway collagen at baseline was positively correlated with pulmonary resistance in asthmatic horses (r(2) = 0.78, P = 0.03) and elastic fiber content was positively associated with pulmonary elastance in controls (r(2) = 0.95, P = 0.02). No difference between groups was appreciated in PGP and N-α-PGP peptides in BALF. Increased airway wall collagen and elastic fiber content may contribute to residual obstruction in the asthmatic airways.

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Section: Discussionmentioning

confidence: 98%

Airway collagen and elastic fiber content correlates with lung function in equine heaves

Setlakwe

Lemos

Lavoie-Lamoureux

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Several molecules, including chemokines, cytokines, and eicosanoids, have been identified in greater concentrations in BALF of heaves‐affected horses compared with normal horses. CXCL8, LTB 4 , and MIP‐2 are three of the most potent chemoattractants synthesized by neutrophils and other cells that have been associated with heaves . IL‐4 and TNF‐α also contribute to recruitment and retention of neutrophils into inflammatory sites .…”

Section: Discussionmentioning

confidence: 99%

“…CXCL8, LTB 4 , and MIP-2 are three of the most potent chemoattractants synthesized by neutrophils and other cells that have been associated with heaves. [29][30][31][32][33][34] IL-4 and TNF-a also contribute to recruitment and retention of neutrophils into inflammatory sites. 35,36 TNF-a induces an increase in the expression of the adhesion molecule ICAM-1 in both human endothelial and bronchial epithelial cells in vitro, which may foster local neutrophil influx in vivo.…”

Section: Discussionmentioning

confidence: 99%

PI3K andMAPKs Regulate Neutrophil Migration Toward the Airways in Heaves

Bullone

Moran

Lavoie‐Lamoureux

et al. 2012

Veterinary Internal Medicne

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Background: Neutrophils accumulate in the airways of horses with heaves. They likely play an important role in the disease pathogenesis. Understanding the pathways regulating their migration may help identifying new therapeutic targets.Hypothesis: MAPK and PI3K pathways are involved in neutrophil migration toward the airway lumen in heaves. Animals: Twelve heaves-affected horses and 4 healthy horses.Methods: Migratory activity of bronchoalveolar lavage fluids (BALF) from horses with heaves and healthy horses was compared by means of a Boyden chamber. Involvement of MAPK and PI3K pathways in neutrophil migration was investigated by pretreating neutrophils with inhibitors of p38 MAPK, JNK, MEK1/2, and PI3K. The capacity of a p38 MAPK inhibitor at decreasing neutrophil chemotaxis toward the airways was also evaluated in vivo.Results: BALF from symptomatic heaves-affected horses induced a greater degree of chemokinesis (P = .0004) than BALF from healthy horses. Although all pathways tested were involved in neutrophil migration, inhibition of PI3K was most potent in vitro. An inhibitor of p38 MAPK administered before challenge in horses with heaves did not alter BALF chemokinetic properties. BALF neutrophil percentage and BALF migratory activity were positively correlated after 14 and 35 days of antigen challenge in healthy (P = .05; R 2 = 0.82) and heaves-affected horses (P = .03; R 2 = 0.76), respectively. Conclusions and Clinical Importance: MAPK and PI3K pathways regulate neutrophil migration induced by BALF of horses with heaves. Inhibition of multiple pathways might be required to completely abolish BALF-induced neutrophil migratory activity and possibly inflammation in heaves.

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“…The immunologic background of severe equine asthma remains not fully elucidated despite many studies on the pathogenesis [38–41] and the therapeutic approach to exacerbation [42–53]. Although evidence for a Th-2 based hypersensitivity reaction of allergy type IV tends to overwhelm [54–56], there is also evidence for a Th-1 based immunologic background of the disease.…”

Section: Local Inflammatory Markers In Tw and Balfmentioning

confidence: 99%

Pulmonary Remodeling in Equine Asthma: What Do We Know about Mediators of Inflammation in the Horse?

Barton

Gehlen

2016

Mediators of Inflammation

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Equine inflammatory airway disease (IAD) and recurrent airway obstruction (RAO) represent a spectrum of chronic inflammatory disease of the airways in horses resembling human asthma in many aspects. Therefore, both are now described as severity grades of equine asthma. Increasing evidence in horses and humans suggests that local pulmonary inflammation is influenced by systemic inflammatory processes and the other way around. Inflammation, coagulation, and fibrinolysis as well as extracellular remodeling show close interactions. Cytology of bronchoalveolar lavage fluid and tracheal wash is commonly used to evaluate the severity of local inflammation in the lung. Other mediators of inflammation, like interleukins involved in the chemotaxis of neutrophils, have been studied. Chronic obstructive pneumopathies lead to remodeling of bronchial walls and lung parenchyma, ultimately causing fibrosis. Matrix metalloproteinases (MMPs) are discussed as the most important proteolytic enzymes during remodeling in human medicine and increasing evidence exists for the horse as well. A systemic involvement has been shown for severe equine asthma by increased acute phase proteins like serum amyloid A and haptoglobin in peripheral blood during exacerbation. Studies focusing on these and further possible inflammatory markers for chronic respiratory disease in the horse are discussed in this review of the literature.

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Evaluation of leukotriene biosynthetic capacity in lung tissues from horses with recurrent airway obstruction

Cited by 6 publications

References 34 publications

Airway collagen and elastic fiber content correlates with lung function in equine heaves

Airway collagen and elastic fiber content correlates with lung function in equine heaves

PI3K andMAPKs Regulate Neutrophil Migration Toward the Airways in Heaves

Pulmonary Remodeling in Equine Asthma: What Do We Know about Mediators of Inflammation in the Horse?

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