Clearance deficiency—A potential link between infections and autoimmunity☆
Section snippets
Apoptosis and the progression to secondary necrosis
Apoptosis—the programmed and natural form of cell death—plays a pivotal role in embryogenesis, development and homeostasis of multicellular organisms. In each moment new cells develop and at the same time other cells must die. After cell shrinkage, chromatin condensation, and DNA cleavage, cellular material gets packed into membrane-derived apoptotic bodies or blebs. These are usually rapidly and efficiently engulfed by neighbouring cells or macrophages in tissues. Notably, during this highly
Molecules involved in phagocytosis of dying cells
Dying cells make use of “find-me”- and “eat-me”-signals for an efficient recognition and engulfment by phagocytes. One “find-me”-signal secreted by apoptotic cells is the soluble lysophosphatidylcholine (LPC) [4]. Exposed and oxidised phosphatidylserine (PS) represents an early “eat-me”-signal. Phagocyte receptors such as CD36, oxLDL receptor, and Mer Kinase bind to PS via several bridging molecules like growth arrest-specific gene 6 (Gas6), milk fat globule EGF/factor VIII (MFG-E8),
Clearance deficiencies, inflammation, and SLE
If invading pathogens are not eliminated or cleared they may cause infection and inflammation. Similarly, if clearance of apoptotic cells is deficient, dying cells will progress to secondary necrosis and leak modified autoantigens, putative “non-self” material, and danger signals. Inflammatory responses or autoimmune reactions as well as chronic autoimmune diseases such as SLE may be the consequences.
SLE is a multifactorial systemic disease. Environmental factors (such as UV radiation or viral
Take-home messages
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Apoptosing cells are cleared in an efficient and silent manner by phagocytes with the support of “find-me”- and “eat-me”-signals.
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The alteration of the glycosylation pattern during apoptosis may serve as “late back-up-eat-me signal”.
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The altered surface of late apoptotic cells results from a substitution of internal ER-membranes after the process of blebbing.
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Clearance deficiency may lead to the accumulation of nuclear material and may thus provoke autoimmunity, as in SLE disease.
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Clearance may
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Grant support: This work was supported by “Deutsche Forschungsgemeinschaft” SFB 643 (project B5), by the European Commissions [E.U. (QLK3-CT-2002-02017_APOCLEAR)], by the Lupus Erythemathodes Selbsthilfegemeinschaft e.V., by the Programme Alban, the European Union Program of High Level Scholarships for Latin America, scholarships no. E04D047956VE to L. E. M. and E07D400430VE to R.A.C. Part of this work was funded by an intramural grant from the ELAN fond and the Training Grant GK592 from the German Research Community (DFG) to C.S and K.S.