Anti-Inflammatory and Immunosuppressive Effects of Recombinant Soluble Complement Receptors

Dt, Fearon

doi:10.1111/j.1365-2249.1991.tb06206.x

Cited by 22 publications

(2 citation statements)

References 18 publications

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“…The effects on tissue injury of decompletnentation with CVF depend on the stage of the model at which CVF is administered, with significant exacerbation of tissue injury being seen when it is given on day 5, so that animals are decomplemented during the middle 5 days of the response. Other more subtle methods of complement inhibition, such as the administration of soluble complement receptors [22], would be required to examine further the role of complement in the effector arm of tissue injury in this model. However, our data suggest that therapeutic strategies aimed at the complement system are unlikely to be helpful in this model, nor, by analogy, in human diseases in which tissue injur>' is due to necrotizing leucocytociastic vasculitis.…”

Section: Discussionmentioning

confidence: 99%

Effects of decomplementation with cobra venom factor on experimental vasculitis

Mathieson

Qasim

Thiru

et al. 1994

Clinical and Experimental Immunology

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SUMMARYMercuric chloride (HgCl2) induces autoimmunity in susceptible rat strains, with hyper-IgE, appearance of a number of autoantibodies. and wide.spread tissue itijury, including necrotizing vasculitis in the gut. In the early phase of tissue injury there is granulocyte infiltration; later there is immunoglobulin deposition along basement membranes in vessels. We have analysed the role of complement in this model using cobra venom factor (CVF). which causes decomplcineniation lasting around 5 days. The characteristic time course when HgCU is given over 10 days is that tissue injury and autoantibody levels reach a peak at around day 15 (start of HgCl2 ^ day 0). We therefore gave CVF either early (day 0). intermediate (day 5) or late (day 10); a fourth group (controls) received HgCli but no CVF. At each time point, CVF caused complete decomplementation which lasted for al least 5 days, Serutn IgE and autoantibody levels were similar in all four experimental groups. Tissue injury in the 'early" CVF group and in Ihe 'Jale' CVF group was not significanlly different from coniroh, but in Ihc intermediate group tissue injury was significantly more severe than in controls. These data indicate that the complement system does not play a major rote in the induction of atitoantibodies by HgCli, nor in the efTeetor phase of tissue injury. We speculate thai the exacerbation of tissue injury by CVF in the group given this agent al an intermediate stage of the model is explained by the presence of products of C3 activation which have proinflammatory effects during the phase of active granulocytc-mcdiated ti.sstje injury.

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Section: Discussionmentioning

confidence: 99%

Effects of decomplementation with cobra venom factor on experimental vasculitis

Mathieson

Qasim

Thiru

et al. 1994

Clinical and Experimental Immunology

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“…The existence of deficiencies and genetic variation in these proteins has been noted above. The use of soluble or engineered forms of complement regulators as potential therapeutic agents is comparatively recent and has been reviewed [25–27] and has progressed in somewhat unexpected ways. It was, for example, not entirely obvious that the most structurally elaborated complement regulator, CR1 (CD35), would be the basis of the first specific biopharmaceutical anti‐complement agent.…”

Section: Therapeutic Intervention In the Complement Systemmentioning

confidence: 99%

Taking Complement to the Clinic – has the Time Finally Come?

Lachmann

Smith

2009

Scand J Immunol

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Complement has been studied for over a century and its role in promoting the effector side of antibody‐mediated immune reactions and of inducing inflammation is well understood. Nevertheless, it has proved surprisingly difficult to translate this information into pharmaceutical agents that can be used to treat immunopathological and inflammatory disease. There are, however, now clear signs that this situation will change. New types of therapeutic agents to interfere with complement function are being developed and it has become apparent quite recently that some common and otherwise untreatable diseases such as age‐related macular degeneration are very largely due to mutations in the complement system that leads to a hyperinflammatory state. This has stimulated a renaissance of interest in the complement system as a therapeutic target and in this short review we discuss the possible ways of taking complement to the clinic, and the indications for which this may be carried out.

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Complement Receptors in Shock and Transplantation

Deitch¹

1993

Arch Surg

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Over the last decade, elegant studies of the basic biologic characteristics of inflammation and tissue injury have implicated leukocyte-mediated vascular and tissue injury in the pathogenesis of a wide variety of immune and inflammatory clinical disorders, including allograft rejection, adult respiratory distress syndrome, and shock. Recognition of the importance of leukocyte adherence to the endothelium in the pathogenesis of these disorders, in combination with advances in cellular and molecular biology, have led to the development of novel therapeutic approaches to the treatment of immune and inflammatory disorders in which leukocytes contribute to vascular and tissue injury. Several of these promising new therapeutic approaches have focused on the complement system. Examples of this therapeutic approach include the use of monoclonal antibodies directed at leukocyte complement receptors and the administration of soluble complement receptors to inhibit the binding of leukocytes to the endothelium. Because of the biologic and significant potential clinical importance of these advances, in this review, we focus on the complement system and complement receptor-mediated tissue injury.

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Anti-Inflammatory and Immunosuppressive Effects of Recombinant Soluble Complement Receptors

Cited by 22 publications

References 18 publications

Effects of decomplementation with cobra venom factor on experimental vasculitis

Effects of decomplementation with cobra venom factor on experimental vasculitis

Taking Complement to the Clinic – has the Time Finally Come?

Complement Receptors in Shock and Transplantation

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