Oxygen radicals mediate endothelial cell damage by complement-stimulated granulocytes. An in vitro model of immune vascular damage.

Sacks, Thomas; Moldow, Charles F.; Craddock, Philip R.; Bowers, Timothy K.; Jacob, Harry S.

doi:10.1172/jci109031

Cited by 1,036 publications

(335 citation statements)

References 30 publications

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“…It has also been suggested that 02-is cytotoxic for autologous red blood cells (48) and human vascular endothelial cells in culture (49). Thus this activated metabolite of PMN, which is associated with increased adherence, may play a role in tissue damage including the vasculitis which is a manifestation of these diseases.…”

Section: Discussionmentioning

confidence: 99%

Increased endothelial cell adherence, aggregation, and superoxide generation by neutrophils incubated in systemic lupus erythematosus and felty's syndrome sera

Hashimoto

Ziff

Hurd

1982

Arthritis & Rheumatism

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The ability of sera from patients with systemic lupus erythematosus (SLE) and Felty's syndrome to induce increased adhesiveness of normal human neutrophils (PMN) was investigated. PMN from normal healthy donors were incubated in sera from 19 patients with active SLE, 12 with inactive SLE, 20 with Felty's, 24 with rheumatoid arthritis, and 34 normal persons. After incubation, the degree of adherence of the PMN to human endothelial cells in culture, their aggregation, and superoxide (O2‐) generation were determined. Sera from patients with both active SLE and Felty's syndrome induced significantly increased PMN adherence to endothelial cells and PMN aggregation in vitro, compared with normal sera. This increased adherence to endothelial cells was maintained after heat treatment (56°C for 30 minutes) of the sera. In O2‐ generation experiments, sera from patients with active SLE induced significantly increased O2‐ release from normal PMN using both fresh and heat‐treated sera. Sera from Felty's patients demonstrated the same effect with heattreated sera but not with fresh sera. When sera from patients with active SLE and Felty's syndrome were used, all three parameters correlated significantly with each other in individual patients. In contrast, sera from the 12 patients with inactive SLE and 24 rheumatoid arthritis patients without Felty's failed to induce significant differences in the three parameters studied when compared with 34 normal controls. Fractionation of 3 SLE sera and 1 Felty's serum on Sephadex G‐200 demonstrated that the adherence enhancing factor was present in both IgG and IgG‐excluded fractions. The observed increased adhesiveness of PMN induced by SLE and Felty's sera may, at least in part, contribute to the neutropenia which is common in these diseases. Increased O2‐ release associated with PMN adherence may contribute to endothelial cell damage and vascular injury, which is also a common manifestation of these diseases.

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Section: Discussionmentioning

confidence: 99%

Increased endothelial cell adherence, aggregation, and superoxide generation by neutrophils incubated in systemic lupus erythematosus and felty's syndrome sera

Hashimoto

Ziff

Hurd

1982

Arthritis & Rheumatism

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“…Superoxide has been shown to play a central role in neutrophil mediated cytotoxicity toward bystander target cells (9) and has been implicated in mediating endothelial cell damage by complement-stimulated granulocytes (10). Whether these observed effects are due to the direct toxic actions of superoxide radicals or are mediated indirectly through reaction products of superoxide, such as hydrogen peroxide, hydroxyl radical, or singlet oxygen (3), remains to be elucidated.…”

Section: -5mentioning

confidence: 99%

“…Recently, superoxide radicals have been implicated as playing an important role in neutrophi1 mediated cytotoxicity (9) and in causing endothelial damage by complement-stimulated granulocytes (10). In addition, superoxide is generated by neutrophils adherent to aggregated IgG-coated filters, a model of immune complex disease (7).…”

mentioning

confidence: 99%

Chemotactic factor‐induced generation of superoxide radicals by human neutrophils

Simchowitz

Mehta

Spilberg

1979

Arthritis & Rheumatism

140

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“…Binding of adenosine or selective agonists through the AZA receptor induces an anti-inflammatory response likely through a cyclic adenosine monophosphate (CAMP) dependent pathway [41]. Activation through the AZA adenosine receptor on PMNLs decreases adherence of activated PMNLs to endothelium [6,41], decreases reactive oxygen radical release [ 1, 4,5,7,22,27,29,, restores cytokine-inhibited PMNL migration [38], and reduces primary lysosome degranulation [2,26,45]. In a rat meningitis model, a selective adenosine AlA receptor agonist decreased WBC chemotaxis and blood brain barrier permeability in response to a lipopolysaccharide (LPS) challenge [41].…”

Section: Introductionmentioning

confidence: 99%

Reducing joint destruction due to septic arthrosis using an adenosine_2A receptor agonist

Cohen

Gill

Baer

et al. 2004

Journal Orthopaedic Research

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We assessed the efficacy of a new adenosine AZA agonist ATL146e, a potent inhibitor of white blood cell chemotaxis, to reduce cartilage damage in the treatment of septic arthrosis. A live septic arthrosis model was created using Staphylococcus aureus in rabbit knees. Animals were divided into five treatment groups: (1) untreated infected control, (2) antibiotics control, and antibiotics plus ATL146e for (3) 24, (4) 48, or (5) 72 h and assessed at I , 4, and 7 days.Knees in all ATL 146e treated animals exhibited no detectable effusion, and histologic examination revealed near normal cartilage and diminished synovial inflammatory response. Synovial WBC counts decreased with the addition of ATL146e when compared to infected and antibiotic controls. Histologic grading of osteochondral specimens demonstrated improved scores for animals treated with ATLl46e compared to infected (p < 0.00004) and antibiotics controls (p < 0.05). Analysis of glycosaminoglycan content revealed significantly decreased loss of articular cartilage following infection in the ATL 146e groups when compared to infected (p < 0.03) and antibiotics controls (p < 0.05).Addition of an adenosine AZA agonist to antibiotic therapy decreases joint inflammation and articular cartilage destruction without compromising bacterial clearance in rabbit knees following intraarticular bacterial infection. The use of adenosine agonists selective to the AZA receptor to augment conventional treatment of joint sepsis may be chondroprotective and ultimately help prevent arthrosis.

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Oxygen radicals mediate endothelial cell damage by complement-stimulated granulocytes. An in vitro model of immune vascular damage.

Cited by 1,036 publications

References 30 publications

Increased endothelial cell adherence, aggregation, and superoxide generation by neutrophils incubated in systemic lupus erythematosus and felty's syndrome sera

Increased endothelial cell adherence, aggregation, and superoxide generation by neutrophils incubated in systemic lupus erythematosus and felty's syndrome sera

Chemotactic factor‐induced generation of superoxide radicals by human neutrophils

Reducing joint destruction due to septic arthrosis using an adenosine_2A receptor agonist

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Oxygen radicals mediate endothelial cell damage by complement-stimulated granulocytes. An in vitro model of immune vascular damage.

Cited by 1,036 publications

References 30 publications

Increased endothelial cell adherence, aggregation, and superoxide generation by neutrophils incubated in systemic lupus erythematosus and felty's syndrome sera

Increased endothelial cell adherence, aggregation, and superoxide generation by neutrophils incubated in systemic lupus erythematosus and felty's syndrome sera

Chemotactic factor‐induced generation of superoxide radicals by human neutrophils

Reducing joint destruction due to septic arthrosis using an adenosine2A receptor agonist

Contact Info

Product

Resources

About

Reducing joint destruction due to septic arthrosis using an adenosine_2A receptor agonist