The complement system is a bridge connecting the innate and adaptive immunity. Excepting the immune defense function (mainly against foreign invaders by opsonization and cytolysis), its multiple functions extend to the surveillance of organism, removal of apoptotic cells and debris, modulation of metabolic and regenerative processes, tumor immune surveillance, and regulation of adaptive immunity.
Inflammatory Disease
The enzymatic cascade is under tight regulation by several mechanisms to avoid disruption of the balance between complement activation and regulation. The imbalance is involved in the pathogenesis of several diseases and disease states. There is an increasing appreciation that complement dysregulation lies at the heart of numerous inflammatory disorders.
The complement components integrally participate in various steps of an inflammatory reaction, which can explain its involvement in the pathogenesis of inflammatory disorders in a manner. The contribution of complement to the pathogenesis of inflammatory diseases can be viewed from various perspectives.
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Activation of Complement
During an inflammatory reaction, the activation of complement contributes to inflammation-driven tissue injury, which occurs in the ischemia/reperfusion (I/R) setting, vasculitides of various etiologies, nephritis, and arthritis. Following IR damages, all three complement activation pathways are involved in the initiation of the proteolytic cleavage of the complement cascade.
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Deficiency in Complement
The deficiency in complement connatural components, or the necessary proteins for efficient complement activation, may also lead to tissue injury, as observed in autoimmune reactions.
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Alterations of Complement Regulatory Proteins
The alterations in the expression of complement regulatory proteins will lead to excessive complement activation, can also contribute to tissue injury.
Fig.1 Complement acts as an important mediator in physiological and pathophysiological processes. (Daniel, et al. 2013)
Recent studies have demonstrated that complement components are engaged in the regulation of all phases of acute inflammatory reaction in different mechanisms:
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The changes in vascular flow and caliber
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The increase in vascular permeability
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The extravasation of leukocytes
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Chemotaxis
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Influence on other inflammatory mediators
Because of its various functions in inflammatory diseases, complement and its inhibitors are being evaluated as new therapeutic options in various clinical programs. Creative Biolabs provides a series of therapeutic antibodies, inhibitors, soluble complement regulators, as well as customized services based for the complement-associated inflammatory disease targets, including:
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Pyoderma gangrenosum
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Salpingo-oophoritis
Our comprehensive complement platform offers a great number of complement-related products in a rapid and cost-effective manner. If you are interested, please feel free to contact us for more details.
Reference
1. Daniel, R.; John, D. L. (2013). Complement in Immune and Inflammatory Disorders: Pathophysiological Mechanisms. The Journal of Immunology. 190(8), 3831-3838.
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Questions & Answer
A: Potential targets include C3, C5, and various complement receptors. Experimental evidence comes from in vitro studies, animal models, and clinical trials with complement inhibitors. Experimental approaches often involve techniques such as ELISA, flow cytometry, Western blotting, and animal models to assess complement activation and its impact on inflammatory diseases.
A: Challenges include the complexity of the complement system, species-specific differences, and the need to mimic human disease in animal models. Ethical and regulatory considerations can also be limiting factors.
A: Animal models especially mice and rats are commonly used, and researchers employ assays to measure complement activation, inflammatory markers, tissue damage, and overall disease progression.
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