The Role of the Anaphylatoxins in Health and Disease

By A. Klos, A. Tenner, Kay O. Johswich, Rahasson R. Ager, Edimara S. Reis, J. Köhl. Molecular Immunology, 2009

720 citations recorded by the source corpus.

The anaphylatoxins (AT) C3a, C5a and C5a-desArg are generally considered pro-inflammatory polypeptides generated after proteolytic cleavage of C3 and C5 in response to complement activation. Their well appreciated effector functions include chemotaxis and activation of granulocytes, mast cells and macrophages. Recent evidence suggests that ATs are also generated locally within tissues by pathogen-, cell-, or contact system-derived proteases. This local generation of ATs is important for their pleiotropic biologic effects beyond inflammation. The ATs exert most of the biologic activities through ligation of three cognate receptors, i.e. the C3a receptor, the C5a receptor and the C5a receptor-like, C5L2. Here, we will discuss recent findings suggesting that ATs regulate cell apoptosis, lipid metabolism as well as innate and adaptive immune responses through their impact on antigen-presenting cells and T cells. As we will outline, such regulatory functions of ATs and their receptors play important roles in the pathogenesis of allergy, autoimmunity, neurodegenerative diseases, cancer and infections with intracellular pathogens.

Subfields: Genetics, Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/3621889b1c2a47457a0753f91bb0197f144945a5

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In Immunology

1. G. Hajishengallis
2. Beth Stevens
3. John D Lambris
4. B. Barres

In Molecular Biology

1. Beth Stevens
2. John D Lambris
3. A. Stephan
4. B. Barres
5. G. Hajishengallis

Citations in the corpus

• Complement System Part I – Molecular Mechanisms of Activation and Regulation (2015, background): “These small (10–14 kDa) peptides play a critical role in supporting inflammation and activation of cells that express anaphylatoxin receptors (250).”
• Complement System Part II: Role in Immunity (2015, background): “C3a and C5a are able to induce potent inflammatory pathways via their receptors C3aR and C5aR.”
• The complement system: an unexpected role in synaptic pruning during development and disease. (2012, background): “Much like C3a, C5a is also a potent neuroinflammatory anaphylatoxin that recruits cells expressing C5a receptors, such as macrophages in the periphery and microglia in the brain (Klos et al 2009, Zhou 2011).”
• Complement - a key system for immune surveillance and homeostasis (2010, background): “Anaphylatoxins are highly potent effectors and have a number of crucial roles in immune responses and inflammation, which are discussed below and reviewed elsewher”
• The Complement System (2010, background): “The anaphylatoxins C3a and C5a, which consist of 77 and 74 amino acids, respectively (Klos et al. 2009), exert a multitude of effects in inflammatory responses.”