Inhibition of complement alternative pathway function with anti-properdin monoclonal antibodies

Gupta-Bansal, Rekha; Parent, J B; Brunden, Kurt R.

doi:10.1016/s0161-5890(00)00047-x

Cited by 37 publications

(42 citation statements)

References 46 publications

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“…Many polymers are known to activate the alternative pathway, and previous reports that a monoclonal anti-properdin Ab is able to block alternative pathway activation in an in vitro model of cardiopulmonary bypass (41) are in accordance with the properdin dependence of the C3,Bb convertase that we have observed. We have also shown in the present study that precoating of the polystyrene with fibrinogen could completely block the adsorption of C3 and therefore the formation of the convertase complexes.…”

Section: Discussionsupporting

confidence: 91%

C3 Adsorbed to a Polymer Surface Can Form an Initiating Alternative Pathway Convertase

Andersson

Ekdahl

Larsson

et al. 2002

The Journal of Immunology

136

109

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Contact between blood and a biomaterial surface induces an immediate complement-mediated inflammatory response. Under these conditions, the alternative pathway of complement is often initiated and amplified on the biomaterial surface. Adsorption of a protein such as C3 to a polymer surface induces conformational changes in the protein. Based on the expression on adsorbed C3 of conformational neoepitopes specific for bound C3 fragments, we have hypothesized that adsorbed C3 is able to bind factor B and form a functional C3,Bb convertase. Using a quartz crystal microbalance to monitor binding of proteins to a polymer surface, we have demonstrated that a functional C3-containing alternative pathway convertase can be formed, in particular, in the presence of properdin. These data indicate that adsorption of C3 induces conformational changes that turn C3 into a C3b-like molecule that is able to participate in the functioning of the alternative convertase, and they suggest a new mechanism for complement activation on a biomaterial surface.

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Section: Discussionsupporting

confidence: 91%

C3 Adsorbed to a Polymer Surface Can Form an Initiating Alternative Pathway Convertase

Andersson

Ekdahl

Larsson

et al. 2002

The Journal of Immunology

136

109

View full text Add to dashboard Cite

show abstract

“…Even though properdin is not an active component of the C3 convertase, it is essential for the stabilization and full activity of the convertase (19,26). Gupta-Bansal et al and Perdikoulis et al (26,27) have demonstrated that Abs directed against properdin are capable of inhibiting the alternative pathway.…”

Section: Discussionmentioning

confidence: 99%

“…Gupta-Bansal et al and Perdikoulis et al (26,27) have demonstrated that Abs directed against properdin are capable of inhibiting the alternative pathway. Recent studies have also shown that properdin is capable of binding to cell surfaces and initiating the alternative pathway by providing a platform for the assembly of the C3 convertase (28).…”

Section: Discussionmentioning

confidence: 99%

A Novel Mechanism of Complement Inhibition Unmasked by a Tick Salivary Protein That Binds to Properdin

Tyson

Elkins

Silva

2008

The Journal of Immunology

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Ixodes scapularis salivary protein 20 (Salp20) is a member of the Ixodes scapularis anti-complement protein-like family of tick salivary proteins that inhibit the alternative complement pathway. In this study, we demonstrate that the target of Salp20 is properdin. Properdin is a natural, positive regulator of the alternative pathway that binds to the C3 convertase, stabilizing the molecule. Salp20 directly bound to and displaced properdin from the C3 convertase. Displacement of properdin accelerated the decay of the C3 convertase, leading to inhibition of the alternative pathway. S20NS is distinct from known decay accelerating factors, such as decay accelerating factor, complement receptor 1, and factor H, which directly interact with either C3b or cleaved factor B.

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“…At least one antibody directed against properdin is currently undergoing testing (145). In experimental studies, this antiproperdin monoclonal antibody was shown to be beneficial during coronary artery bypass grafting, reducing the activation of platelets and neutrophils (163).…”

Section: Immunomodulation Of Complementmentioning

confidence: 99%

New Insights of an Old Defense System: Structure, Function, and Clinical Relevance of the Complement System

Ehrnthaller

Ignatius

Gebhard

et al. 2010

Mol Med

190

154

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The complement system was discovered a century ago as a potent defense cascade of innate immunity. After its first description, continuous experimental and clinical research was performed, and three canonical pathways of activation were established. Upon activation by traumatic or surgical tissue damage, complement reveals beneficial functions of pathogen and danger defense by sensing and clearing injured cells. However, the latest research efforts have provided a more distinct insight into the complement system and its clinical subsequences. Complement has been shown to play a significant role in the pathogenesis of various inflammatory processes such as sepsis, multiorgan dysfunction, ischemia/reperfusion, cardiovascular diseases and many others. The three well-known activation pathways of the complement system have been challenged by newer findings that demonstrate direct production of central complement effectors (for example, C5a) by serine proteases of the coagulation cascade. In particular, thrombin is capable of producing C5a, which not only plays a decisive role on pathogens and infected/damaged tissues, but also acts systemically. In the case of uncontrolled complement activation, "friendly fire" is generated, resulting in the destruction of healthy host tissue. Therefore, the traditional research that focuses on a mainly positive-acting cascade has now shifted to the negative effects and how tissue damage originated by the activation of the complement can be contained. In a translational approach including structure-function relations of this ancient defense system, this review provides new insights of complement-mediated clinical relevant diseases and the development of complement modulation strategies and current research aspects.

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Inhibition of complement alternative pathway function with anti-properdin monoclonal antibodies

Cited by 37 publications

References 46 publications

C3 Adsorbed to a Polymer Surface Can Form an Initiating Alternative Pathway Convertase

C3 Adsorbed to a Polymer Surface Can Form an Initiating Alternative Pathway Convertase

A Novel Mechanism of Complement Inhibition Unmasked by a Tick Salivary Protein That Binds to Properdin

New Insights of an Old Defense System: Structure, Function, and Clinical Relevance of the Complement System

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