Enzymatic inactivation of human alpha-1-proteinase inhibitor by neutrophil myeloperoxidase

Matheson, Nancy; Wong, P.S.; Travis, James

doi:10.1016/0006-291x(79)92062-x

Cited by 250 publications

(102 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(20) could act as a substrate for the myeloperoxidase system of PMN to form, in the presence of chloride anions, hypochlorous acid, a powerful oxidizing agent (63). In vitro studies have shown that methionines in alPI are oxidized and the alPI is inactivated in vitro by all of these oxidants: stimulated PMN preparations (64), a combination of H202 and O2 generated by xanthine oxidase (65), and the myeloperoxidase system (66,67). A second major pathway for cigarette smoke-induced inactivation of alPI is the direct oxidation of alPI by components in the smoke itself.…”

Section: The Tar Radical(s) In Cigarette Smoke: Esr Studiesmentioning

confidence: 99%

Free-Radical Chemistry of Cigarette Smoke and Its Toxicological Implications

Church¹,

Pryor²

1985

Environmental Health Perspectives

330

297

View full text Add to dashboard Cite

Cigarette smoke contains two very different populations of free radicals, one in the tar and one in the gas phase. The tar phase contains several relatively stable free radicals; we have identified the principal radical as a quinone/hydroquinone (Q/QH2) complex held in the tarry matrix. We suggest that this Q/QH2 polymer is an active redox system that is capable of reducing molecular oxygen to produce superoxide, eventually leading to hydrogen peroxide and hydroxyl radicals. In addition, we have shown that the principal radical in tar reacts with DNA in vitro, possibly by covalent binding.The gas phase of cigarette smoke contains small oxygen-and carbon-centered radicals that are much more reactive than are the tar-phase radicals. These gas-phase radicals do not arise in the flame, but rather are produced in a steady state by the oxidation of NO to NO2, which then reacts with reactive species in smoke such as isoprene. We suggest that these radicals and the metastable products derived from these radical reactions may be responsible for the inactivation of a,-proteinase inhibitor by fresh smoke.Cigarette smoke oxidizes thiols to disulfides; we suggest the active oxidants are NO and NO2. The effects of smoke on lipid peroxidation are complex, and this is discussed. We also discuss the toxicological implications for the radicals in smoke in terms of a number of radical-mediated disease processes, including emphysema and cancer.

show abstract

Section: The Tar Radical(s) In Cigarette Smoke: Esr Studiesmentioning

confidence: 99%

Free-Radical Chemistry of Cigarette Smoke and Its Toxicological Implications

Church¹,

Pryor²

1985

Environmental Health Perspectives

330

297

View full text Add to dashboard Cite

show abstract

“…It has been suggested that ROS contribute to aggravation of inflammation by a mechanism in which ROS inactivate endogenous protease inhibitors, thereby allowing NE to attack and degrade tissues [9,18]. In this respect, selection of appropriate animal species may be important in studying the role of NE on colitis, as the anti-NE activity of protease inhibitors and the susceptibility of these inhibitors to ROS vary widely between species.…”

Section: Discussionmentioning

confidence: 99%

“…Release of NE during inflammation is related to degradation of connective tissues and an increase in vascular permeability, thus causing tissue damage and organ failure [4,6]. It has been reported that α1-protease inhibitor (α1-PI), an endogenous inhibitor of NE, is inactivated by reactive oxygen species (ROS) released from neutrophils, resulting in attenuation of the NE inhibitory activity of α1-PI and a consequent increase in NE activity (NE/α1-PI imbalance) that leads to the aggravation of inflammation [9,18]. These processes have been suggested to play an important role in the progression of various inflammatory diseases, such as chronic obstructive pulmonary disease (COPD) and IBD [8,12].…”

mentioning

confidence: 99%

Effects of the Neutrophil Elastase Inhibitor (ONO-6818) on Acetic Acid Induced Colitis in Syrian Hamsters

et al. 2004

View full text Add to dashboard Cite

ABSTRACT. Neutrophil elastase (NE) released from neutrophils during inflammation is related to tissue disturbance and organ failure. We investigated the effects of an orally active NE inhibitor, ONO-6818, on acetic acid induced colitis in Syrian hamsters. The ulcer area, hemoglobin level in the colonic lumen, NE activity, and tissue myeloperoxidase (MPO) activity in the colitis control animals were significantly increased compared to the normal control ones. Either oral or subcutaneous treatment with ONO-6818 had significant inhibitory effects on the ulcer area, hemoglobin level and NE activity in the colonic lumen, but ONO-6818 did not have a significant inhibitory effect on tissue MPO activity. We conclude that NE is closely related to the development of inflammation in acetic acid-induced colitis in Syrian hamsters and that the condition is improved by the inhibition of NE. KEY WORDS: colitis, neutrophil elastase, orally active inhibitor, Syrian hamster.

show abstract

“…Despite an immunologically sufficient concentration of «i.PI we could demonstrate free elastase activity in some exudate samples. Oxidative impairment of o^PI has been described (15) and may be due to the release of myeloperoxidase and highly reactive oxygen products during phagocytosis.…”

Section: Discussionmentioning

confidence: 99%