Complement Activation and Subclassification of Tissue Immunoglobulin G in the Abdominal Aortic Aneurysm

Capella, Joseph F.; Paik, David C.; Yin, N X; Gervasoni, James E.; Tilson, M. David

doi:10.1006/jsre.1996.0339

Cited by 37 publications

(27 citation statements)

References 2 publications

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“…This finding is consistent with previous results of immunoglobulin accumulation in abnormal vascular tissues; abdominal aortic aneurysms show strongly increased amounts of IgG together with complement C3d. 24 Immunoglobulins have been detected earlier in unruptured IA walls in similar proportions as those seen here in both unruptured and ruptured IAs, but not in control basilar artery samples. 8 In atherosclerotic coronary arteries, IgM has been shown to accumulate and colocalize with the classical pathway activation products C4b/iC4b in the superficial intima.…”

Section: Immunoglobulins and Complement Activationsupporting

confidence: 79%

Complement system becomes activated by the classical pathway in intracranial aneurysm walls

Tulamo

Frösén

Junnikkala

et al. 2010

Laboratory Investigation

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Inflammation and activation of the complement system in the intracranial aneurysm (IA) wall predispose to IA rupture. We have previously shown that increased C5b-9 accumulation correlates with IA rupture and wall degeneration. To elucidate the underlying mechanisms, we investigated initiators and the pathway of complement activation in unruptured and ruptured IAs. Unruptured and ruptured IA wall samples were studied in parallel sections by immunohistochemical and immunofluorescence stainings for the location and relations of classical and alternative pathway complement components (C1q, C3b/iC3b, C3d, C4b/iC4b; n ¼ 35 and properdin, n ¼ 10), putative complement activators IgG (n ¼ 90), IgM, CRP and OxLDL (n ¼ 10), and complement activation endproduct C5b-9. Classical pathway components were seen in all IAs, and they were located mostly in the extracellular matrix. The early pathway complement components colocalized with each other, but were present in larger areas than C5b-9. The areas positive for complement component accumulation were significantly broader in ruptured than in unruptured IAs. The potential complement activators IgG, IgM, CRP and OxLDL were found mostly in the extracellular matrix and in partial overlap with C5b-9. Lipids were seen in Oil-Red-O staining in colocalization with C5b-9. Complement becomes activated by the classical pathway in the IA wall. The activation appears to be induced by multiple factors, which, in addition to the traditional activators (immunoglobulins, CRP, OxLDL), could involve vascular pressure-induced tissue damage. Despite wide early pathway activation, the terminal pathway is focused on a distinct lipid-rich layer. The profile of the complement components and the association of C5b-9 with lipids in the extracellular matrix indicate a long-term chronic inflammatory process rather than an acute targeted inflammatory reaction. The observed pattern of complement activation may be the consequence of local stress-induced insufficiency of complement regulation in IA walls. KEYWORDS: aneurysm; complement; CRP; immunoglobulin; inflammation; oxidized LDL Saccular intracranial artery aneurysm (IA) rupture causes subarachnoidal hemorrhage (SAH), with up to 50% mortality. 1 However, the mechanisms behind IA development, structural weakening and rupture are poorly understood. In a meta-analysis, 2.3% (range 0.4-6.0%) of various populations were found to harbor IA. 2 Known risk factors for IA rupture and SAH include smoking, hypertension, previous rupture, female gender, excessive alcohol abuse and family history, but these explain only part of the IA disease. 3,4 Inflammation and its key component complement activation precede IA rupture. Inflammatory cell infiltration and deposits of the activation products of the terminal complement pathway can be found in unruptured IAs. 5-9 Immunoglobulins and pro-inflammatory cytokines (eg, TNF-a) have also been detected in human IAs. 8,10 The IA wall undergoes a remodeling process. This is indicated by the expression of vascular growth factor r...

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Section: Immunoglobulins and Complement Activationsupporting

confidence: 79%

Complement system becomes activated by the classical pathway in intracranial aneurysm walls

Tulamo

Frösén

Junnikkala

et al. 2010

Laboratory Investigation

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“…Capella et al have found that all Ig subclasses are increased in aortic wall extracts of patients with AAA. 70 Among those subclasses, IgG1 and IgG3 may be responsible for activation of complement by the classic pathway, 70 which agrees with the increase in C3 complement fraction in the wall of AAA patients. 70 IgG4, whose levels show the highest increase rate, 70 has been proposed as a candidate mediator in the development of inflammatory AAA.…”

Section: B Cellsmentioning

confidence: 75%

Immune Cells and Molecular Mediators in the Pathogenesis of the Abdominal Aortic Aneurysm

Rizas

Ippagunta²,

Tilson³

2009

Cardiology in Review

134

105

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Abdominal aortic aneurysm is a multifactorial disease with genetic risk factors and an immunologic component. Immune cells, including macrophages, neutrophils, mast cells, B- and T- lymphocytes, along with vascular smooth muscle cells and adventitial fibroblasts, produce cytokines and enzymes, promoting an inflammatory reaction, extracellular matrix degradation, and neovascularization. Among the different enzymes secreted by immune and stromal cells, matrix metalloproteinase (MMP)-2, MMP-9, MMP-12, cathepsins, and neutrophil elastase cause medial degeneration. Chymase causes smooth muscle cell apoptosis, and MMP-3, MMP-8, and MMP-13 cause adventitial collagen degradation, promoting abdominal aortic aneurysm rupture. At the same time chemokines (interleukin 8, macrophage inflammatory protein 1 alpha, monocyte chemotactic protein-1) cause recruitment and proliferation of inflammatory cells, whereas cytokines (vascular endothelial growth factor and transforming growth factor-beta) promote neoangiogenesis.

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“…On the other hand, IgG or IgM activates the complement cascade to produce the membrane attack complex (MAC) that further mediates the inflammatory response [42]. Early in 1995, Joseph et al [43] showed that AAA had increased IgG1, IgG2, IgG3, and complement C3 components compared with aortic occlusive disease and the normal aortic wall. They reasoned that, in AAA, the elevated IgG1, IgG2, and IgG3 levels may be associated with the activation of complement by the classical pathway.…”

Section: The Production Of Immunoglobulinsmentioning

confidence: 98%

B lymphocytes in abdominal aortic aneurysms

Zhang

Wang

2015

Atherosclerosis

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Complement Activation and Subclassification of Tissue Immunoglobulin G in the Abdominal Aortic Aneurysm

Cited by 37 publications

References 2 publications

Complement system becomes activated by the classical pathway in intracranial aneurysm walls

Complement system becomes activated by the classical pathway in intracranial aneurysm walls

Immune Cells and Molecular Mediators in the Pathogenesis of the Abdominal Aortic Aneurysm

B lymphocytes in abdominal aortic aneurysms

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