Regulation of the function of the first component of complement by human C1q receptor

Berg, R.H. van den; Faber-Krol, Maria C.; Es, Leendert A. van; Daha, Mohamed R.

doi:10.1002/eji.1830250814

Cited by 44 publications

(25 citation statements)

References 40 publications

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“…Numerous studies have reported the presence of calreticulin on endothelial cells (50 -53). Calreticulin on the surface of endothelial cells appears to be capable of modulating cell function, because it has been shown that calreticulin is involved in the production of interleukin-8 by human umbilical vein endothelial cells (51). Calreticulin is readily detectable on the surface of resting bone marrow vascular endothelial cells, and its expression is up-regulated in response to inflammatory mediators (53).…”

Section: Discussionmentioning

confidence: 99%

Thrombospondin Mediates Focal Adhesion Disassembly through Interactions with Cell Surface Calreticulin

Goicoechea¹,

Orr²,

Pallero³

et al. 2000

Journal of Biological Chemistry

155

135

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Thrombospondin induces reorganization of the actin cytoskeleton and restructuring of focal adhesions. This activity is localized to amino acids 17-35 in the N-terminal heparin-binding domain of thrombospondin and can be replicated by a peptide (hep I) with this sequence. Thrombospondin/hep I stimulate focal adhesion disassembly through a mechanism involving phosphoinositide 3-kinase activation. However, the receptor for this thrombospondin sequence is unknown. We now report that calreticulin on the cell surface mediates focal adhesion disassembly by thrombospondin/hep I. A 60-kDa protein from endothelial cell detergent extracts has homology and immunoreactivity to calreticulin, binds a hep I affinity column, and neutralizes thrombospondin/ hep I-mediated focal adhesion disassembly. Calreticulin on the cell surface was confirmed by biotinylation, confocal microscopy, and by fluorescence-activated cell sorting analyses. Thrombospondin and calreticulin potentially bind through the hep I sequence, since thrombospondin-calreticulin complex formation can be blocked specifically by hep I peptide. Antibodies to calreticulin and preincubation of thrombospondin/hep I with glutathione S-transferase-calreticulin block thrombospondin/hep I-mediated focal adhesion disassembly and phosphoinositide 3-kinase activation, suggesting that calreticulin is a component of the thrombospondin-induced signaling cascade that regulates cytoskeletal organization. These data identify both a novel receptor for the N terminus of thrombospondin and a distinct role for cell surface calreticulin in cell adhesion.

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Section: Discussionmentioning

confidence: 99%

Thrombospondin Mediates Focal Adhesion Disassembly through Interactions with Cell Surface Calreticulin

Goicoechea¹,

Orr²,

Pallero³

et al. 2000

Journal of Biological Chemistry

155

135

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“…A single 220-kDa band was observed. C1q and MBL were purified from pooled human plasma obtained from healthy donors as described previously (25,26). C3 was purified from serum using different steps of chromatography, whereas C3b was generated by brief trypsin cleavage (60 s) of purified C3 followed by direct inactivation.…”

Section: Isolation Of Properdin C1q and Mbl And C3 And C3bmentioning

confidence: 99%

Properdin Binds to Late Apoptotic and Necrotic Cells Independently of C3b and Regulates Alternative Pathway Complement Activation

Xu¹,

Berger²,

Trouw

et al. 2008

The Journal of Immunology

Self Cite

119

105

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Cells that undergo apoptosis or necrosis are promptly removed by phagocytes. Soluble opsonins such as complement can opsonize dying cells, thereby promoting their removal by phagocytes and modulating the immune response. The pivotal role of the complement system in the handling of dying cells has been demonstrated for the classical pathway (via C1q) and lectin pathway (via mannose-binding lectin and ficolin). Herein we report that the only known naturally occurring positive regulator of complement, properdin, binds predominantly to late apoptotic and necrotic cells, but not to early apoptotic cells. This binding occurs independently of C3b, which is additional to the standard model wherein properdin binds to preexisting clusters of C3b on targets and stabilizes the convertase C3bBb. By binding to late apoptotic or necrotic cells, properdin serves as a focal point for local amplification of alternative pathway complement activation. Furthermore, properdin exhibits a strong interaction with DNA that is exposed on the late stage of dying cells. Our data indicate that direct recognition of dying cells by properdin is essential to drive alternative pathway complement activation.

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“…The rationale for this assay is based on the observation that HuCRT does not interact with Ig-bound C1q when C1r 2 C1s 2 are already associated (22,59). The assay requires purified C1q to be added back to C1q-deficient serum, to reconstitute the C1 complex.…”

Section: Rtccrt and Its Tcs And Tccrt R Domains Inhibit The Classicalmentioning

confidence: 99%

The Classical Activation Pathway of the Human Complement System Is Specifically Inhibited by Calreticulin from Trypanosoma cruzi

Ferreira¹,

Valck²,

Sánchez

et al. 2004

The Journal of Immunology

124

141

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The high resistance of Trypanosoma cruzi trypomastigotes, the causal agent of Chagas’ disease, to complement involves several parasite strategies. In these in vitro studies, we show that T. cruzi calreticulin (TcCRT) and two subfragments thereof (TcCRT S and TcCRT R domains) bind specifically to recognition subcomponents of the classical and lectin activation pathways (i.e., to collagenous tails of C1q and to mannan-binding lectin) of the human complement system. As a consequence of this binding, specific functional inhibition of the classical pathway and impaired mannan-binding lectin to mannose were observed. By flow cytometry, TcCRT was detected on the surface of viable trypomastigotes and, by confocal microscopy, colocalization of human C1q with surface TcCRT of infective trypomastigotes was visualized. Taken together, these findings imply that TcCRT may be a critical factor contributing to the ability of trypomastigotes to interfere at the earliest stages of complement activation.

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Regulation of the function of the first component of complement by human C1q receptor

Cited by 44 publications

References 40 publications

Thrombospondin Mediates Focal Adhesion Disassembly through Interactions with Cell Surface Calreticulin

Thrombospondin Mediates Focal Adhesion Disassembly through Interactions with Cell Surface Calreticulin

Properdin Binds to Late Apoptotic and Necrotic Cells Independently of C3b and Regulates Alternative Pathway Complement Activation

The Classical Activation Pathway of the Human Complement System Is Specifically Inhibited by Calreticulin from Trypanosoma cruzi

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