Kinetics of equine neutrophil elastase release and superoxide anion generation following secretagogue activation: a potential mechanism for antiproteinase inactivation

Dagleish, Mark P.; Pemberton, Alan D.; Brazil, Timothy J.; McALEESE, Sybil M.; Miller, H. R. P.; Scudamore, Cheryl L.

doi:10.1016/s0165-2427(99)00144-0

Cited by 17 publications

(27 citation statements)

References 53 publications

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“…Exposure to a greater organic dust load may result in a more severe inflammatory response leading to oxidative stress. Equine peripheral blood neutrophils have been demonstrated to contain approximately 0.8 pg ENE 2A=cell [16]. In the present study, the median ENE 2A concentration and neutrophil number in BALF for the RAO group were 20.6 ng=mL and 186 neutrophils=mL, respectively, at the end of the exposure period.…”

Section: Discussionsupporting

confidence: 45%

“…Venous blood samples were analyzed for ascorbic acid, DHA, uric acid, and thiobarbituric acid-reactive substances (TBARSs) in plasma, and reduced (GSH) and oxidized (GSSG) glutathione in red blood cell hemolysate as described previously [18]. BALF was centrifuged at 800 Â g for 10 minutes at 4 C. ENE 2A concentrations were determined by a specific sandwich enzyme-linked immuno sorbent assay (ELISA) [16] on BALF supernatant, which had been stored at À80 C prior to analysis. BALF supernatant was also analyzed for reduced ascorbic acid, DHA, total ascorbic acid (reduced ascorbic acid and DHA), uric acid, GSH, GSSG, total glutathione (GSH and GSSG), malondialdehyde (MDA), and total protein [18] and data are presented per liter of BALF supernatant [20].…”

Section: Sample Analysismentioning

confidence: 99%

“…We therefore hypothesized that ascorbic acid would be the primary antioxidant consumed during an acute period of neutrophilic airway inflammation and the degree of oxidative stress produced would correlate with the decrease in BALF ascorbic acid concentration and decrements in lung function. The inflammatory response to organic dust inhalation was not only determined by cytological analysis of BALF samples, but also by measuring the concentration of equine neutrophil elastase 2A (ENE 2A), the most abundant equine neutrophil elastase [16], in BALF as a marker of neutrophil degranulation.…”

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confidence: 99%

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Effect of Acute Airway Inflammation on the Pulmonary Antioxidant Status

Deaton

Marlin

Smith

et al. 2005

Experimental Lung Research

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Effects of acute airway inflammation induced by organic dust inhalation on pulmonary antioxidant status were investigated in healthy horses and horses affected by recurrent airway obstruction. Exposure to organic dust induced acute airway neutrophilia, which was associated with increases in elastase and decreases in ascorbic acid concentrations in bronchoalveolar lavage fluid. However, markers of oxidative stress were unaffected, as was hydrogen peroxide in breath condensate. Decreases in ascorbic acid correlated with increased respiratory resistance (P = .001) when both groups were combined. In conclusion, acute neutrophilic airway inflammation does not result in significant evidence of oxidative stress in horses affected by recurrent airway obstruction.

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Section: Discussionsupporting

confidence: 45%

Section: Sample Analysismentioning

confidence: 99%

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confidence: 99%

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Effect of Acute Airway Inflammation on the Pulmonary Antioxidant Status

Deaton

Marlin

Smith

et al. 2005

Experimental Lung Research

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“…Dagleish et al (1999) have shown that activated horse and human neutrophils concurrently release ROS, elastase and antiproteinase. However, in human beings, the antiproteinase released by the neutrophil may be locally destroyed by ROS that are also produced by the neutrophil.…”

Section: Figmentioning

confidence: 99%

Ischemia in equine intestine – mechanisms of injury and methods of treatment

Freeman¹,

Grosche²

2012

PHK

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SummaryThe importance of reperfusion injury in equine intestine is controversial and unclear. Large colon volvulus and small intestinal strangulation are the most devastating causes of intestinal ischemia in horses and result in severe mucosal damage, barrier dysfunction, endotoxic shock and death. Although essential for tissue recovery, reperfusion after these types of ischemia could exacerbate intestinal injury. Responses to ischemia and reperfusion (I/R) involve a series of synchronized biochemical, cellular and structural changes characterized by generation of reactive oxygen metabolites, activation of immune cells, and epithelial cell degeneration and death. The intensity of neutrophil activation and influx is central to the process of reperfusion injury and the associated inflammatory events. The classic paradigm of reperfusion injury is best displayed after the segmental hypoperfusion or low-flow ischemia model, in which arterial inflow is adjusted to 20% of normal baseline flow, and then allowed to return to normal or greater values during reperfusion. In such cases, injury during the ischemic phase is mild, compared with the reperfusion injury that follows. Although there is some evidence of reperfusion injury in equine colon and jejunum after low-flow ischemia, attempts to ameliorate this by pharmacologic means have met with only moderate success. A multimodal approach, using solutions designed to improve survival in transplanted organs, seems to hold the greatest promise, although these have not been embraced in the clinical setting. Expense and difficulties in delivery are the two most serious limitations. Recent studies to assess the effect of colonic I/R on equine pelvic flexure involved a complete ischemia model that was similar to the clinical lesion, and for periods of 1 to 2 hours of ischemia followed by 30 minutes, 4 hours, or 18 hours of reperfusion. Ischemia caused degeneration and detachment of epithelial cells, early apoptosis, and opening of tight junctions (TJs), all of which decreased transepithelial resistance (TER) and increased mannitol flux when the tissues were studied in vitro. Autophagy was a prominent feature in epithelial cells after 1 hour of ischemia. Reperfusion was characterized by apoptosis, epithelial regeneration, and closure of TJs with improved TER and reduced mannitol leakage. Neutrophils infiltrated colonic mucosa during reperfusion, and macrophages, mast cells and eosinophils were activated during I/R. Equine colonic mucosa subjected to ischemia can repair rapidly and regain barrier integrity during reperfusion, despite intense mucosal inflammation. Recently, attention has focused on inflammation induced by intestinal handling and on remote organ responses to intestinal injury, both of which could be highly relevent to postoperative management of horses that undergo colic surgery. The use of lidocaine in a continuous rate infusion is a popular approach to ameliorate the intestinal inflammatory response after colic surgery, although there is no evidence that it has a...

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“…In horses, the typing of the protease inhibitor system is more complex. Identification of Spi variants using electrophoresis and the measurements of serum Spi concentration by ELISA are not considered ideal procedures (Dagleish et al, 1999(Dagleish et al, , 2000, and the molecular sequence of each Spi has still not been fully determined. It therefore appears that there is a need to establish more efficient methods to identify the genetic variants derived from each Spi (Godard et al, 1998;Milenkovic et al, 2002) in order to clarify the role of this locus in the onset of equine COPD.…”

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confidence: 99%

Equine protease inhibitor system as a marker for the diagnosis of chronic obstructive pulmonary disease (COPD)

et al. 2005

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The protease inhibitor system (PI) was investigated to ascertain if it can be used as a marker of chronic obstructive pulmonary disease (COPD) in thoroughbred horses. Serum samples were taken from healthy thoroughbreds (n = 13) and those diagnosed as having COPD (n = 24) or inflammatory airway disease (IAD, n = 38) as well as from 3,600 undiagnosed thoroughbred horses. PI allelic and genotypic frequencies were estimated using protein electrophoresis on starch and polyacrylamide gels. The four groups of horses showed high genotypic similarity and none of the observed alleles or genotypes of the equine PI system were found to be associated with COPD.

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Kinetics of equine neutrophil elastase release and superoxide anion generation following secretagogue activation: a potential mechanism for antiproteinase inactivation

Cited by 17 publications

References 53 publications

Effect of Acute Airway Inflammation on the Pulmonary Antioxidant Status

Effect of Acute Airway Inflammation on the Pulmonary Antioxidant Status

Ischemia in equine intestine – mechanisms of injury and methods of treatment

Equine protease inhibitor system as a marker for the diagnosis of chronic obstructive pulmonary disease (COPD)

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