Degradation of glycosaminoglycans by reactive oxygen species derived from stimulated polymorphonuclear leukocytes

The chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) has been shown to constrict both bronchial and coronary vascular smooth muscle through the action of cyclooxygenase or lipoxygenase products. We observed that intravenous FMLP increased pulmonary vascular resistance (PVR) in isolated buffer-perfused rabbit lungs. FMLP increased the PVR (primarily in the middle segment of the pulmonary vascular bed) at concentrations greater than or equal to 10(-7) M. Maximum vasoconstriction occurred at 5 min and then slowly declined to a level that remained above baseline at 30 min. Tachyphylaxis was observed in response to FMLP. When polymorphonuclear leukocytes (PMNs) were added to the perfusate, FMLP caused a greater increase in PVR. PMN depletion with dimethylmyleran significantly reduced the PVR response to FMLP. Pretreatment with two dissimilar cyclooxygenase inhibitors, meclofenamate and ibuprofen, and the leukotriene synthesis blocker MK 886 had no effect on the FMLP-induced vasoconstriction. However, the reactive oxygen species scavenger catalase significantly reduced the vasoconstriction. These results suggest that FMLP induces vasoconstriction that is dependent on PMNs and mediated by reactive oxygen species with no involvement of cyclooxygenase or lipoxygenase products.

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ChemInform Abstract: Effects of BX661A (I), a New Therapeutic Agent for Ulcerative Colitis, on Chemotaxis and Reactive Oxygen Species Production in Polymorphonuclear Leukocytes in Comparison with Salazosulfapyridine and Its Metabolite Sulfapyridine.

ChemInform ◽

10.1002/chin.199913118 ◽

2010 ◽

Vol 30 (13) ◽

pp. no-no

Author(s):

Isami Kimura ◽

Maki Kawasaki ◽

Akihiko Matsuda ◽

Mikiko Kataoka ◽

Yukifumi Kokurba

Keyword(s):

Reactive Oxygen Species ◽

Ulcerative Colitis ◽

Polymorphonuclear Leukocytes ◽

Reactive Oxygen Species Production ◽

Therapeutic Agent ◽

Reactive Oxygen ◽

Oxygen Species ◽

Species Production

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Human Leukocytes KillAspergillus nidulansby Reactive Oxygen Species-Independent Mechanisms

Infection and Immunity ◽

10.1128/iai.00921-10 ◽

2010 ◽

Vol 79 (2) ◽

pp. 767-773 ◽

Cited By ~ 30

Author(s):

Stefanie S. V. Henriet ◽

Peter W. M. Hermans ◽

Paul E. Verweij ◽

Elles Simonetti ◽

Steven M. Holland ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Nadph Oxidase ◽

Polymorphonuclear Leukocytes ◽

Mononuclear Cells ◽

Reactive Oxygen ◽

Healthy Controls ◽

Oxygen Species ◽

Peripheral Blood Mononuclear ◽

Antifungal Effects

ABSTRACTInvasive aspergillosis is a major threat for patients suffering from chronic granulomatous disease (CGD). AlthoughAspergillus fumigatusis the most commonly encounteredAspergillusspecies, the presence ofA. nidulansappears to be disproportionately high in CGD patients. The purpose of this study was to investigate the involvement of the NADPH oxidase and the resulting reactive oxygen species (ROS) in host defense against fungi and to clarify their relationship towardA. nidulans. Murine CGD alveolar macrophages (AM) and polymorphonuclear leukocytes (PMN) and peripheral blood mononuclear cells (PBMC) from healthy controls and CGD patients were challenged with eitherA. fumigatusorA. nidulans. Analysis of the antifungal effects of ROS revealed thatA. nidulans, in contrast toA. fumigatus, is not susceptible to ROS. In addition, infection with liveA. nidulansdid not result in any measurable ROS release. Remarkably, human CGD PMN and PBMC and murine CGD AM were at least equipotent at arresting conidial germination compared to healthy controls. Blocking of the NADPH oxidase resulted in significantly reduced damage ofA. fumigatusbut did not affectA. nidulanshyphae. Furthermore, the microbicidal activity of CGD PMN was maintained towardA. nidulansbut notA. fumigatus. In summary, antifungal resistance toA. nidulansis not directly ROS related. The etiology ofA. nidulansinfections in CGD cannot be explained by the simple absence of the direct microbicidal effect of ROS.In vivo, the NADPH oxidase is a critical regulator of innate immunity whose unraveling will improve our understanding of fungal pathogenesis in CGD.

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