Neutrophil elastase and oxygen radicals: synergism in lung injury after hindlimb ischemia

Welbourn, C. R. B.; Goldman, Gideon; Paterson, Ian; Valeri, C. R.; Shepro, David; Hechtman, Herbert B.

doi:10.1152/ajpheart.1991.260.6.h1852

Cited by 42 publications

(38 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Reperfusion injury is characterized by leukocyte recruitment resulting in tissue dysfunction in various organ systems including heart, skeletal muscle, lungs, intestine, and skin (20)(21)(22)(23)(24). Leukocyte-endothelium interaction involves initial rolling (repeated transient contacts) of leukocytes along the endothelial surface followed by their firm adhesion and diapedesis.…”

mentioning

confidence: 99%

Hypoxia/reoxygenation causes inflammatory response in transgenic sickle mice but not in normal mice

2000

View full text Add to dashboard Cite

mentioning

confidence: 99%

Hypoxia/reoxygenation causes inflammatory response in transgenic sickle mice but not in normal mice

2000

View full text Add to dashboard Cite

“…Infiltrating leukocytes have been implicated as key mediators of ischemia/reperfusion injury associated with the heart (1, 2), brain (3), intestine (4,5), skeletal muscle (6), and various other tissues (7)(8)(9). This contention is based primarily on three pieces of evidence; (a) leukocytes infiltrate postischemic tissue (1, 2, 5), (b) leukocyte depletion from the circulation reduces reperfusion-induced tissue injury (2,4), and (c) reagents that interfere with leukocyte infiltration into postischemic vessels concomitantly provide protection against reperfusion injury (7,(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Therapeutic potential of inhibiting leukocyte rolling in ischemia/reperfusion.

Kubes¹,

Jutila²,

Payne³

1995

J. Clin. Invest.

242

147

View full text Add to dashboard Cite

Leukocyte rolling has been postulated to be mandatory for subsequent leukocyte adhesion and tissue injury observed during ischemia/reperfusion. The objective of this study was to systematically assess this hypothesis at the microvascular level by examining the effects of various concentrations of a selectin-binding carbohydrate (fucoidin) on the increased rolling and adhesion of leukocytes in postischemic venules. The contribution of L-selectin and/or P-selectin to leukocyte rolling were also assessed in this model. Using intravital microscopy we observed that 60 min of ischemia followed by reperfusion caused a profound increase in leukocyte rolling and adhesion. A high dose of fucoidin (25 mg/kg) reduced leukocyte rolling by > 90% and significantly reduced leukocyte adhesion, whereas a lower dose of fucoidin still reduced leukocyte rolling by 60% but had no effect on leukocyte adhesion. Moreover, despite the profound reduction in leukocyte rolling with fucoidin, the remaining rolling cells were able to firmly adhere via a CD18-dependent mechanism, particularly in those postcapillary venules with reduced (30-50%) shear rates. The increased rolling was also reduced 60% by either an anti-P-selectin antibody, an anti-L-selectin antibody, or a combination of the two antibodies, but this reduction in rolling cells did not translate into significantly reduced leukocyte adhesion. Our data suggest that L-selectin, P-selectin, and a fucoidin-sensitive pathway contribute to the significant increase in reperfusion-induced leukocyte rolling. However, targeting leukocyte rolling as a form of therapy requires very significant efficacy (> 90%) to achieve reasonable (-50%) attenuation in leukocyte adhesion in postischemic venules. (J. Clin. Invest. 1995Invest. . 95:2510Invest. -2519

show abstract

“…However, the precise role of neutrophil elastase in the early stage of the acute lung inflammation has not yet been evaluated. In previous studies of specific elastase inhibitors in several models of lung inflammation, endotoxin was found to cause endothelial cell injury and was almost completely inhibited by elastase inhibitors [16][17][18]. Furthermore, GOSSAGE et al [24] have shown that the synthetic neutrophil elastase inhibitors SC-37698 and SC-39026 reduce endotoxin-induced lung dysfunction in sheep [24].…”

mentioning

confidence: 99%

“…Thus, neutrophils appear to play a major role in LPS-induced lung inflammation [13][14][15]. Most previous studies of proteinase involvement in lung inflammation have focused on neutrophil elastase [16][17][18][19][20][21], since neutrophil elastase is prominent in the BAL fluid of such patients [22,23]. However, the precise role of neutrophil elastase in the early stage of the acute lung inflammation has not yet been evaluated.…”

mentioning

confidence: 99%

A specific neutrophil elastase inhibitor (ONO-5046.Na) attenuates LPS-induced acute lung inflammation in the hamster

Yasui¹,

Nagai²,

Aoshiba³

et al. 1995

Eur Respir J

View full text Add to dashboard Cite

A A s sp pe ec ci if fi ic c n ne eu ut tr ro op ph hi il l e el la as st ta as se e i in nh hi ib bi it to or r ( (O ON NO O--5 50 04 46 6 · ·N Na a) )a at tt te en nu ua at te es s L LP PS S--i in nd du uc ce ed d a ac cu ut te e l lu un ng g i in nf fl la am mm ma at ti io on n i in n t th he e h ha am ms st te er r Syrian golden hamsters were injected intraperitoneally with either 300 mg·kg -1 of ONO-5046·Na or saline, 30 min before and 1 h after intratracheal administration of 0.1 mg·kg -1 LPS. Animals were sacrificed 2 and 24 h later and the wet-todry lung weight ratio (W/D) was determined. Bronchoalveolar lavage (BAL) was performed, and tissue sections were examined histologically. The effect of ONO5046·Na on migration of isolated neutrophils was determined. W/D was not significantly different at 2 h, but was increased at 24 h in the LPStreated animals. This increase was attenuated in the LPS-treated animals injectedwith ONO-5046·Na. Analysis of BAL fluid revealed that both at 2 and 24 h after LPS administration the total cell number and neutrophil number, albumin concentration, and elastase-like activity were significantly lower in the LPS-treated animals injected with ONO-5046·Na than in those given LPS alone. Histological examination of the lungs of the animals treated with LPS alone showed intraalveolar haemorrhages and inflammatory cell infiltration 24 h after LPS administration, whereas the lungs of the LPS-treated ONO-5046·Na injected animals were only sparsely infiltrated by inflammatory cells, as indicated by the inflammation score.Although ONO-5046·Na had no effect on neutrophil migration in vitro; the present findings suggest that ONO-5046·Na attenuates LPS-induced acute lung inflammation by inhibiting neutrophil migration in vivo, and conversely that neutrophil elastase plays a considerable role in the pathogenesis of the acute lung inflammation induced by LPS.

show abstract

Neutrophil elastase and oxygen radicals: synergism in lung injury after hindlimb ischemia

Cited by 42 publications

References 20 publications

Hypoxia/reoxygenation causes inflammatory response in transgenic sickle mice but not in normal mice

Hypoxia/reoxygenation causes inflammatory response in transgenic sickle mice but not in normal mice

Therapeutic potential of inhibiting leukocyte rolling in ischemia/reperfusion.

A specific neutrophil elastase inhibitor (ONO-5046.Na) attenuates LPS-induced acute lung inflammation in the hamster

Contact Info

Product

Resources

About