Terminal complement complexes concomitantly stimulate proliferation and rescue of Schwann cells from apoptosis

Dashiell, Suzanne M.; Rus, Horea; Koski, Carol Lee

doi:10.1002/(sici)1098-1136(200004)30:2<187::aid-glia8>3.0.co;2-7

Cited by 43 publications

(27 citation statements)

References 61 publications

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“…This resulted in transition from the G 1 to S phase, with consequent increases in cell proliferation (55). Similar MAC-driven proliferation occurs in endothelial cells (56) and Schwann cells (57).…”

Section: Complement Promotes Oncogenesismentioning

confidence: 68%

Cancer and the Complement Cascade

Rutkowski

Sughrue

Kane

et al. 2010

Molecular Cancer Research

225

249

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Despite significant research on the role of inflammation and immunosurveillance in the immunologic microenvironment of tumors, little attention has been given to the oncogenic capabilities of the complement cascade. The recent finding that complement may contribute to tumor growth suggests an insidious relationship between complement and cancer, especially in light of evidence that complement facilitates cellular proliferation and regeneration. We address the hypothesis that complement proteins promote carcinogenesis and suggest mechanisms by which complement can drive the fundamental features of cancer. Evidence shows that this diverse family of innate immune proteins facilitates dysregulation of mitogenic signaling pathways, sustained cellular proliferation, angiogenesis, insensitivity to apoptosis, invasion and migration, and escape from immunosurveillance. Given that the traditionally held functions for the complement system include innate immunity and cancer defense, our review suggests a new way of thinking about the role of complement proteins in neoplasia.

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Section: Complement Promotes Oncogenesismentioning

confidence: 68%

Cancer and the Complement Cascade

Rutkowski

Sughrue

Kane

et al. 2010

Molecular Cancer Research

225

249

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“…S5). Previous reports using non-T cells have also demonstrated cellular proliferation in response to nonlytic C5b-9 (48,49).…”

Section: Perm Both Naive Cd4mentioning

confidence: 82%

T Cell Activation by Terminal Complex of Complement and Immune Complexes

Chauhan

Moore

2011

Journal of Biological Chemistry

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T cell hyperactivation and complement consumption are prominent features of the immunopathology of systemic lupus erythematosus. Although complement activation is secondary to autoantibodies that form immune complexes (ICs), the trigger for alterations in human peripheral blood T cells is poorly understood. To study the impact (on T cells) of several types of preformed ICs and terminal complement complex, also referred to as C5b-9, we incubated these immune reactants with peripheral blood naive CD4؉ T cells as well as Jurkat cells and analyzed their effects on cellular behavior. We first assembled the C5b-9 in situ on the membrane and observed its assembly primarily on a single site where it promoted aggregation of membrane rafts and recruitment of the CD3 signaling complex. However, C5b-9 alone did not initiate proliferation or commencement of downstream signaling events associated with T cell activation. When T cells were treated with ICs together with nonlytic C5b-9, changes associated with T cell activation by possible antigen engagement then occurred. T cell antigen receptor signaling proteins, including -chain, ZAP-70, Syk, Src, and Lck, were phosphorylated and organized in a synapse-like structure. The cytoskeleton formed F-actin spindles and a distal pole complex, resulting in a bipolar distribution of phosphorylated ezrin-radixin-moesin and F-actin. Furthermore, ICs and nonlytic C5b-9 induced T cell proliferation and IFN-␥ production. These results raise the possibility that ICs and the nonlytic C5b-9 modulate T cell-mediated responses in systemic lupus erythematosus and other related chronic inflammatory disorders.

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“…The C5b-9 membrane attack complex has been implied to play a role both as protector from apoptosis (sublytic complex; Refs. [55][56][57] and as an inductor of apoptosis (58 -60). Thus, the complement system seems involved in many aspects of apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Vitamin K-Dependent Protein S Localizing Complement Regulator C4b-Binding Protein to the Surface of Apoptotic Cells

Webb

Blom

Dahlbäck

2002

The Journal of Immunology

103

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Apoptosis is characterized by a lack of inflammatory reaction in surrounding tissues, suggesting local control of complement activation. During the initial stage of apoptosis, cells expose negatively charged phospholipid phosphatidylserine on their surfaces. The vitamin K-dependent protein S has a high affinity for this type of phospholipid. In human plasma, 60–70% of protein S circulates in complex with C4b-binding protein (C4BP). The reason why protein S and C4BP form a high-affinity complex in plasma is not known. However, C4BP is an important regulator of the classical pathway of the complement system where it acts as a cofactor in degradation of complement protein C4b. Using Jurkat cells as a model system for apoptosis, we now show protein S to bind to apoptotic cells. We further demonstrate protein S-mediated binding of C4BP to apoptotic cells. Binding of the C4BP-protein S complex to apoptotic cells was calcium-dependent and could be blocked with Abs directed against the phospholipid-binding domain in protein S. Annexin V, which binds to exposed phosphatidylserine on the apoptotic cell surface, could inhibit the binding of protein S. The C4BP that was bound via protein S to the apoptotic cells was able to interact with the complement protein C4b, supporting a physiological role of the C4BP/protein S complex in regulation of complement on the surface of apoptotic cells.

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Terminal complement complexes concomitantly stimulate proliferation and rescue of Schwann cells from apoptosis

Cited by 43 publications

References 61 publications

Cancer and the Complement Cascade

Cancer and the Complement Cascade

T Cell Activation by Terminal Complex of Complement and Immune Complexes

Vitamin K-Dependent Protein S Localizing Complement Regulator C4b-Binding Protein to the Surface of Apoptotic Cells

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