Functional heterogeneity of anti-endothelial cell antibodies

Bordron, Anne; Révélen, R; d’Arbonneau, Frédérique; Dueymes, Maryvonne; Renaudineau, Yves; Jamin, Christophe; Youinou, Pierre

doi:10.1046/j.1365-2249.2001.01528.x

Cited by 47 publications

(33 citation statements)

References 43 publications

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“…35 Alternatively, overall reduction of AECAs, as shown by suppressed immunoreactive luminal rat IgG in the ESb group, could have reduced local activation or apoptosis of endothelial cells 36,37 and prevented strokes. 38 E-selectin tolerization may also have suppressed local activity of a functional T-cell subset associated with ischemia in unstable angina, the IFN-␥-secreting CD4 ϩ CD28 null NK-T cells. 39 Although the precise molecular mechanisms for the strong stroke prevention conferred by mucosal tolerization to E-selectin remain to be clarified, the overall effect of this intervention is to target immunosuppression to activated vessel segments.…”

Section: Endothelial Cells That Have Been Activated By Ifn-␥ (Perhapsmentioning

confidence: 99%

Induction of Mucosal Tolerance to E-Selectin Prevents Ischemic and Hemorrhagic Stroke in Spontaneously Hypertensive Genetically Stroke-Prone Rats

Takeda

Spatz

Ruetzler

et al. 2002

Stroke

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Background and Purpose-Inflammatory and immune mechanisms can precipitate cerebrovascular thrombosis and hemorrhage. Immunologic tolerance can be induced to a specific antigen by intranasal instillation of that antigen. Lymphocytes tolerized in this way provide local immunosuppression on restimulation with the same antigen. This study tests whether tolerization of lymphocytes to E-selectin can suppress local vessel activation and prevent stroke. Methods-Spontaneously hypertensive genetically stroke-prone rats (nϭ113) were distributed among the following studies: comparison of ischemic infarcts/intraparenchymal hemorrhages after single or repetitive tolerization schedules with ovalbumin, E-selectin, or PBS; comparison of E-selectin tolerization-and PBS tolerization-induced suppression of delayed-type hypersensitivity in animals subsequently sensitized to E-selectin; and comparison of PBS-, ovalbumin-, and E-selectin-tolerized groups (after intravenous lipopolysaccharide to activate vessels) regarding transforming growth factor-␤1-positive splenocyte counts, plasma interferon-␥ levels, anti-human E-selectin antibodies, endothelial intercellular adhesion molecule-1, and anti-endothelial cell antibodies. Results-Nasal instillation of E-selectin, which is specifically expressed on activated endothelium, potently inhibited the development of ischemic and hemorrhagic strokes in spontaneously hypertensive stroke-prone rats with untreated hypertension. Repeated schedules of tolerization were required to maintain the resistance to stroke. Suppression of delayed-type hypersensitivity to E-selectin and increased numbers of transforming growth factor-␤1-positive splenocytes showed that intranasal exposure to E-selectin induced immunologic tolerance. E-selectin tolerization also reduced endothelial activation and immune responses after intravenous lipopolysaccharide, as shown by marked suppression of intercellular adhesion molecule-1 expression, anti-endothelial cell antibodies on luminal endothelium, and plasma interferon-␥ levels compared with the control condition. Key Words: E-selectin Ⅲ endothelium Ⅲ immune tolerance Ⅲ risk factors Ⅲ rats A t blood vessel segments, inflammatory and immune reactions that lead to the local release of proinflammatory cytokines and local activation of luminal endothelium can initiate stroke. 1,2 In atherosclerosis, these multipotent autocrine or paracrine mediators can regulate the expression of leukocyte adhesion molecules, the production of other cytokines, growth factors, and chemokines, and the production of matrix metalloproteinases. 3 Local endothelium integrates extracellular signals and cellular responses in different regions of the vascular tree. 4 Occasional perivascular ring patterns of immunoreactive tumor necrosis factor (TNF)-␣, heme oxygenase-1, and manganese superoxide dismutase in brain parenchyma of normal rats reflect cyclic activation and inactivation of brain vessel segments. 5 Conclusions-The See Editorial Comment, page 2163These cycles appear to be more frequent and...

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Section: Endothelial Cells That Have Been Activated By Ifn-␥ (Perhapsmentioning

confidence: 99%

Induction of Mucosal Tolerance to E-Selectin Prevents Ischemic and Hemorrhagic Stroke in Spontaneously Hypertensive Genetically Stroke-Prone Rats

Takeda

Spatz

Ruetzler

et al. 2002

Stroke

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“…In vasculitides, it was suggested that endothelium was not only the target of injury, but also an active participant of vasculitic damage [9]. Anti-endothelial cell antibodies (AECA) have been described in various autoimmune and vasculitic disorders [10][11][12][13][14][15][16][17][18]. They have been implicated in the pathogenesis of vascular injury common to these disorders.…”

Section: Introductionmentioning

confidence: 99%

Anti-endothelial cell antibodies (AECA) in patients with propylthiouracil (PTU)-induced ANCA positive vasculitis are associated with disease activity

Zhao

Zhang

et al. 2005

Clinical and Experimental Immunology

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SummaryIncreasing evidence has demonstrated that propylthiouracil (PTU) could induce ANCA positive vasculitis. However, our previous work has suggested that only one-fifth of the PTU-induced ANCA positive patients had clinical vasculitis and so the mechanism is not clear. Anti-endothelial cell antibodies (AECA) have been implicated in the pathogenesis of various vasculitides, including primary ANCA positive systemic vasculitis. The purpose of this study is to investigate the prevalence of AECA and their possible role in the pathogenesis of patients with PTU-induced ANCA positive vasculitis. Sera from 11 patients with PTU-induced ANCA positive vasculitis at both active and quiescent phases, and sera from 10 patients with PTU-induced ANCA but without clinical vasculitis, were studied. Sera from 30 healthy blood donors were collected as normal controls. Soluble proteins from 1% Triton-100 extracted in vitro cultured human umbilical vein endothelial cells were used as antigens and an immunoblotting technique was performed to determine the presence of AECA, and their specific target antigens were identified. In patients with PTU-induced ANCA positive vasculitis, 10 of the 11 patients in an active phase of disease were serum IgG-AECA positive and six protein bands of endothelial antigens could be blotted (61 kD, 69 kD, 77 kD, 85 kD, 91 kD and 97 kD). However, in the quiescent phase, seven of the 10 positive sera turned negative. None of the ANCA positive but vasculitis negative patients or normal controls were AECA positive. In conclusion, AECA could be found in sera from patients with PTU-induced ANCA positive vasculitis and were associated more closely with vasculitic disease activity.

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“…The cell ELISA for AECAs has been described previously (3,4,26,27). Briefly, EA.hy926 cells were fixed with 1% glutaraldehyde for 10 min at 4°C.…”

Section: Methodsmentioning

confidence: 99%

“…A recent experimental model of systemic vasculitis has, based on auto-Ab idiotype, provided compelling evidence suggesting that some AECAs are pathogenic (5). Current efforts have focused on the EC activation of type II, which would be elicited by this or another group of AECAs (4). Evidence for such an activation includes upregulation of adhesion molecules, e.g., E-selectin and intercellular adhesion molecule 1 (ICAM-1).…”

mentioning

confidence: 99%

Effects of Anti-Endothelial Cell Antibodies in Leprosy and Malaria

et al. 2004

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As a result of damaging endothelial cells (ECs), Mycobacterium leprae triggers the production of antibodies (Abs). These anti-EC Abs (AECAs) can be divided into two types. The first type nonspecifically reacts with components of the cytosol (CY) and can be detected by enzyme-linked immunosorbent assay (ELISA). The second specifically reacts with the EC membrane (MB) and requires fluorescence-activated cell sorter (FACS) analysis to be detected. The presence of both types of AECAs was determined in 68 leprosy patients. The ELISA was positive for 35 of them but also for 30 of 34 malaria patients and 17 of 50 healthy African controls. However, whereas FACS analysis showed MB reactivity in only three malaria patients and four controls, this reactivity was found in 27 leprosy patients, more of those having the lepromatous than the tuberculoid form. Specificity for MB, which we failed to absorb by incubation with CY lysates, predominated over that for CY in leprosy, unlike malaria, where the EC reactivity was restricted to the CY. Western blot analysis and twodimensional electrophoresis revealed that calreticulin, vimentin, tubulin, and heat shock protein 70 were targeted by AECAs from leprosy patients, but other proteins remained unidentified. These auto-Abs, but not those from malaria patients, did activate ECs, as indicated by the E-selectin and intercellular adhesion molecule 1 upregulation, and/or induced them into apoptosis, as documented by four different methods. Our findings suggest that, in some but not all leprosy patients, AECAs may play a role in pathogenesis.

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Functional heterogeneity of anti-endothelial cell antibodies

Cited by 47 publications

References 43 publications

Induction of Mucosal Tolerance to E-Selectin Prevents Ischemic and Hemorrhagic Stroke in Spontaneously Hypertensive Genetically Stroke-Prone Rats

Induction of Mucosal Tolerance to E-Selectin Prevents Ischemic and Hemorrhagic Stroke in Spontaneously Hypertensive Genetically Stroke-Prone Rats

Anti-endothelial cell antibodies (AECA) in patients with propylthiouracil (PTU)-induced ANCA positive vasculitis are associated with disease activity

Effects of Anti-Endothelial Cell Antibodies in Leprosy and Malaria

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