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Research Article Free access | 10.1172/JCI2261

The binding of some human antiendothelial cell antibodies induces endothelial cell apoptosis.

A Bordron, M Dueymes, Y Levy, C Jamin, J P Leroy, J C Piette, Y Shoenfeld, and P Y Youinou

Laboratory of Immunology, "Institut de Synergie des Sciences et de la Santé," Brest University Medical School, F 29 609 Brest, France.

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Laboratory of Immunology, "Institut de Synergie des Sciences et de la Santé," Brest University Medical School, F 29 609 Brest, France.

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Laboratory of Immunology, "Institut de Synergie des Sciences et de la Santé," Brest University Medical School, F 29 609 Brest, France.

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Laboratory of Immunology, "Institut de Synergie des Sciences et de la Santé," Brest University Medical School, F 29 609 Brest, France.

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Laboratory of Immunology, "Institut de Synergie des Sciences et de la Santé," Brest University Medical School, F 29 609 Brest, France.

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Laboratory of Immunology, "Institut de Synergie des Sciences et de la Santé," Brest University Medical School, F 29 609 Brest, France.

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Laboratory of Immunology, "Institut de Synergie des Sciences et de la Santé," Brest University Medical School, F 29 609 Brest, France.

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Laboratory of Immunology, "Institut de Synergie des Sciences et de la Santé," Brest University Medical School, F 29 609 Brest, France.

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Published May 15, 1998 - More info

Published in Volume 101, Issue 10 on May 15, 1998
J Clin Invest. 1998;101(10):2029–2035. https://doi.org/10.1172/JCI2261.
© 1998 The American Society for Clinical Investigation
Published May 15, 1998 - Version history
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Abstract

The pathogenic role of antiendothelial cell antibodies (AECA) remains unclear. They are frequently associated with antibodies to anionic phospholipids (PL), such as phosphatidylserine (PS), which is difficult to reconcile with the distribution of PL molecular species within the plasma membrane. Since it is already known that PS is transferred to the outer face of the membrane as a preclude to apoptosis, the possibility exists that apoptosis is initiated by AECA. AECA-positive/anti-PL antibody-negative sera from eight patients with systemic sclerosis (SS) and 21 control patients were evaluated. Endothelial cells (EC) were incubated with AECA and the exposure of PS was established through the binding of annexin V. Hypoploid cell enumeration, DNA fragmentation, and optical and ultrastructural analyses of EC were used to confirm apoptosis. Incubation of EC with AECA derived from six of eight patients with SS led to the expression of PS on the surface of the cells. This phenomenon was significantly more frequent in SS (P < 0.04) than in control diseases. The redistribution of plasma membrane PS preceded other events associated with apoptosis: hypoploidy, DNA fragmentation, and morphology characteristic for apoptosis. Apoptosis-inducing AECA did not recognize the Fas receptor. We conclude that AECA may be pathogenic by inducing apoptosis.

Version history
  • Version 1 (May 15, 1998): No description
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