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Complement System

The complement system is part of the innate immune system and plays an important role in the host defense, inflammation, tissue regeneration and other physiological processes. Complement activation results in opsonization of pathogens and their removal by phagocytes. It also causes chemotactic attraction of phagocytes and macrophages. Furthermore, the complement system forms the terminal attack complex (MAC), a membrane channel causing osmotic lysis of the respective pathogen. While complement is not adaptable it does complement the adaptive immune system and it is also involved in B and T cell response regulation.

Activation of Complement System

Activation of complement unfolds along three different complement activation pathways depending on the nature of the pathogen: The classical pathway, the lectin pathway, and the alternative pathway. All three converge into the common terminal pathway that leads to the formation of the MAC. In addition, anaphylatoxins C3a and C5a elicit a plethora of physiological responses that range from chemoattraction to apoptosis. The complement system consists of more than 30 proteins that are either present as soluble proteins in the blood or as membrane-associated proteins. Most exist as inactive zymogens that are then sequentially cleaved and activated. The central component in all three pathways is component C3, the most abundant complement protein found in the blood. Its activation induces the formation of the activation products C3a, C3b, and C5a and ultimately the MAC. In addition to these three established pathways, it has been shown that factors such as kallikrein, plasmin, thrombin, and factor XIIa activate the complement system independently of the C3 protein.

Role of Complement System in Disease

Innate immune mechanisms including the complement system are the first line of a higher organism’s defense against infective agents coming from the external environment. Impairment of these basic mechanisms can cause a diverse spectrum of diseases. The reasons for the complement system malfunctioning may be different. They are often the result of mutations in genes encoding the complement cascade proteins or regulatory proteins.

Deficiencies of the C3 and other complement components, contribute to the emergence of recurrent bacterial, viral and fungal infections. MBL also plays a major protective role in the early stages of infection and in the control of inflammation. Its deficit is one of the most common reasons for human immunodeficiency, observed in microbial infections as well as in autoimmune diseases such as rheumatoid arthritis. On the other hand, the excessive activation of complement proteins is often discovered to be the reason for many diseases. These include e.g. autoimmune diseases, Alzheimer's syndrome, schizophrenia, atypical hemolytic-uremic syndrome, angioedema, macular degeneration, and Crohn's disease.

Complement is responsible for immune inflammatory response in adipose tissues which has been implicated in the development of obesity and can lead to tissue inflammation and eventually insulin resistance. Lack of regulation of the classical complement pathway through the deficiency in C1-inhibitor results in episodic angioedema. C1-inhibitor defiency can be hereditary or acquired, resulting in hereditary or acquired angioedema. Addtionally, deficiency in the C1q protein of the classical complement pathway can lead to development of systemic lupus erythematosus.

Immunotherapies have been developed to detect and destroy cells infected by the HIV virus via classical complement activation utilizing synthetic peptides that target conserved regions in HIV specific proteins and induce an antibody specific immune response through IgG antibodies.

In COVID-19, the SARS-CoV-2 nucleocapsid protein triggers activation of the lectin pathway of the complement system through interaction with mannose binding lectin (MBL)-associated serine protease (MASP)2. Released soluble N protein dimers interact with MASP-2, further accelerating MASP-2 activation and activation of the complement system. The positive feedback through cell lysis and release of N-protein leads to elevation of pro-inflammatory cytokines, characterized as cytokine storm.

N-protein neutralization is a promising avenue for a COVID-19 therapy, as well as the targeted inhibition of MASP-2. Suppressive effects could also be observed with anti-C5a antibody treatment.


References:

  1. Edimara S, et al. (2019): "New Insights into the Immune Functions of Complement" Nat Rev Immunol 19(8): 503–516. doi:10.1038/s41577-019-0168-x.
  2. Xaria X Li, et al. (2019): "The Complement Receptor C5aR2: A" Powerful Modulator of Innate and Adaptive Immunity" J Immunol 202:3339-3348. doi: 10.4049/jimmunol.1900371
  3. Vandendriessche S, et al. (2019): "Complement Receptors and Their Role in Leukocyte Recruitment and Phagocytosis" Front. Cell Dev. Biol. 9:624025. doi: 10.3389/fcell.2021.624025
  4. Gao T, et al. (2020): "Highly pathogenic coronavirus N protein aggravates lung injury by MASP-2-mediated complement over-activation" medRxiv, [DOI: 10.1101/2020.03.29.20041962v2]
  5. Risitano AM, et al., (2020): “Complement as a target in COVID-19?” Nature Reviews Immunology, 65(12): 1337-45 [DOI: 10.1038/s41577-020-0320-7]

Complement System Related Proteins

Product
Source
Cat. No.
Validations
Quantity
Delivery
SourceEscherichia coli (E. coli)
Cat. No.ABIN3091778
Validations
  • collections(1)
Quantity1 mg
Delivery30 to 35 Days
SourceEscherichia coli (E. coli)
Cat. No.ABIN4371968
Validations
Quantity50 μg
Delivery4 Days
SourceInsect Cells
Cat. No.ABIN3091707
Validations
  • collections(1)
Quantity1 mg
Delivery50 Days
SourceInsect Cells
Cat. No.ABIN3077730
Validations
  • collections(1)
Quantity1 mg
Delivery70 Days
SourceInsect Cells
Cat. No.ABIN3078028
Validations
  • collections(1)
Quantity1 mg
Delivery50 Days
SourceInsect Cells
Cat. No.ABIN3091807
Validations
  • collections(1)
Quantity1 mg
Delivery70 Days
SourceInsect Cells
Cat. No.ABIN3077789
Validations
  • collections(1)
Quantity1 mg
Delivery50 Days
SourceInsect Cells
Cat. No.ABIN3125981
Validations
  • collections(1)
Quantity1 mg
Delivery50 Days
SourceInsect Cells
Cat. No.ABIN3090455
Validations
  • collections(1)
Quantity1 mg
Delivery50 Days
SourceInsect Cells
Cat. No.ABIN3090385
Validations
  • collections(1)
Quantity1 mg
Delivery50 Days
SourceHuman
Cat. No.ABIN4888419
Validations
Quantity100 μg
Delivery9 to 11 Days

Complement System Related Antibodies

Product
Reactivity
Clonality
Application
Cat. No.
Quantity
ReactivityHuman
ClonalityPolyclonal
ApplicationIHC (p), WB
Cat. No.ABIN657704
Quantity400 μL
ReactivityHuman
ClonalityMonoclonal
ApplicationCoat, ELISA, IHC, StM
Cat. No.ABIN6940808
Quantity100 μg
ReactivityHuman, Rat
ClonalityPolyclonal
ApplicationIHC (p), WB
Cat. No.ABIN2855659
Quantity100 μL
ReactivityHuman
ClonalityPolyclonal
ApplicationELISA, IHC (p), WB
Cat. No.ABIN3181728
Quantity100 μL
ReactivityHuman
ClonalityPolyclonal
ApplicationICC, IF, IHC (p), WB
Cat. No.ABIN2856109
Quantity100 μL
ReactivityHuman
ClonalityPolyclonal
ApplicationID, ELISA, WB
Cat. No.ABIN285285
Quantity500 μL
ReactivityHuman, Mouse
ClonalityPolyclonal
ApplicationELISA, IF (cc), IF (p), IHC (p), WB
Cat. No.ABIN727875
Quantity100 μL
ReactivityHuman
ClonalityPolyclonal
ApplicationFACS, IF, IHC (p), WB
Cat. No.ABIN390924
Quantity400 μL
ReactivityHuman
ClonalityMonoclonal
ApplicationIF, IHC, StM
Cat. No.ABIN6940809
Quantity100 μg

Complement System Related ELISA Kits

Product
Sample Type
Analytical Method
Cat. No.
Validations
Quantity
Sample TypePlasma, Serum
Analytical MethodQuantitative Sandwich ELISA
Cat. No.ABIN6574234
Validations
  • (1)
  • collections(5)
Quantity96 tests
Sample TypeCell Culture Cells, Cerebrospinal Fluid, Milk, Plasma, Saliva, Serum, Urine
Analytical MethodQuantitative Sandwich ELISA
Cat. No.ABIN5564590
Validations
  • collections(1)
Quantity96 tests
Sample TypeCell Culture Supernatant, Cell Lysate, Plasma, Serum, Tissue Homogenate
Analytical MethodQuantitative Sandwich ELISA
Cat. No.ABIN6954999
Validations
  • collections(1)
Quantity96 tests
Sample TypePlasma, Serum
Analytical MethodQuantitative Sandwich ELISA
Cat. No.ABIN6955010
Validations
  • (4)
  • collections(1)
Quantity96 tests
Sample TypePlasma, Serum, Tissue Homogenate
Analytical MethodQuantitative Sandwich ELISA
Cat. No.ABIN6966018
Validations
  • collections(1)
Quantity96 tests
Sample TypeCell Culture Supernatant, Cell Lysate, Plasma, Serum, Tissue Homogenate
Analytical MethodQuantitative Sandwich ELISA
Cat. No.ABIN6955023
Validations
  • (1)
  • collections(1)
Quantity96 tests
Sample TypeCell Culture Supernatant, Plasma, Serum
Analytical MethodQuantitative Sandwich ELISA
Cat. No.ABIN6962118
Validations
  • collections(1)
Quantity96 tests
Sample TypePlasma, Serum
Analytical MethodQuantitative Sandwich ELISA
Cat. No.ABIN6730898
Validations
  • (5)
  • collections(4)
Quantity96 tests
Sample TypeCell Culture Supernatant, Cell Lysate, Plasma, Serum, Tissue Homogenate
Analytical MethodQuantitative Sandwich ELISA
Cat. No.ABIN6955038
Validations
  • (5)
  • collections(1)
Quantity96 tests
Sample TypePlasma, Serum
Analytical MethodQuantitative Sandwich ELISA
Cat. No.ABIN6955046
Validations
  • (6)
  • collections(1)
Quantity96 tests

Classical Pathway

Lectin Pathway

Alternative Pathway

Terminal Pathway

Regulators

Extrinsic Pathway

PRSS57 (Protease, Serine, 57):

Complement Receptors

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