The activation of the complement cascade produces a number of small fragments that are bioactive: potent chemoattractants and secretagogues that act on immune and non-immune cells []. Similar peptides can also be released by the actions of non-complement proteases, for instance during clotting []. Initially these were termed anaphylatoxins because of their effect on mast cell histamine release, but were reclassified as complement component peptides. They include C3a and C5a, which are involved immune response [], neural development and organ regeneration [, ]. A third peptide, C4a, has a similar structure, but it is inactive in humans []. Since the primary function of complement component peptides is in inflammation, they are important targets for the development of anti-inflammatory therapies [].The anaphylatoxin chemotactic receptors (also known as complement peptide receptors) are a group of rhodopsin-like G-protein coupled receptors (GPCRs) [, , , ]. There are three subtypes: C3a anaphylatoxin chemotactic receptor (C3AR1) [], C5a anaphylatoxin chemotactic receptor (C5AR1) []and C5a anaphylatoxin chemotactic receptor C5L2 (C5AR2) []. Both C3AR1 and C5AR1 receptors are classical GPCRs. However, C5AR2 appears to be permanently uncoupled from G proteins but can associate with beta-arrestin []. Nevertheless, it has been shown that activation of both C5AR1 and C5AR2 is required for a full pro-inflammatory response, particularly in mice []. Several receptor antagonists have been reported [, , , ], although none, so far, have been show to be effective in humans. This entry represents C3AR1, also known as complement component 3a receptor 1 and C3aR []. It appears to be widely expressed in different lymphoid tissues, providing evidence for a central role in inflammatory processes []. This receptor stimulates chemotaxis [], granule enzyme release [, ]and increases phosphorylated-ERK1/2 production []. C3AR1 may provide a theraputic avenue for the treatment of asthma [], retinal degeneration [], and rheumatoid arthritis [].
The activation of the complement cascade produces a number of small fragments that are bioactive: potent chemoattractants and secretagogues that act on immune and non-immune cells []. Similar peptides can also be released by the actions of non-complement proteases, for instance during clotting []. Initially these were termed anaphylatoxins because of their effect on mast cell histamine release, but were reclassified as complement component peptides. They include C3a and C5a, which are involved immune response [], neural development and organ regeneration [, ]. A third peptide, C4a, has a similar structure, but it is inactive in humans []. Since the primary function of complement component peptides is in inflammation, they are important targets for the development of anti-inflammatory therapies [].The anaphylatoxin chemotactic receptors (also known as complement peptide receptors) are a group of rhodopsin-like G-protein coupled receptors (GPCRs) [, , , ]. There are three subtypes: C3a anaphylatoxin chemotactic receptor (C3AR1) [], C5a anaphylatoxin chemotactic receptor (C5AR1) []and C5a anaphylatoxin chemotactic receptor C5L2 (C5AR2) []. Both C3AR1 and C5AR1 receptors are classical GPCRs. However, C5AR2 appears to be permanently uncoupled from G proteins but can associate with beta-arrestin []. Nevertheless, it has been shown that activation of both C5AR1 and C5AR2 is required for a full pro-inflammatory response, particularly in mice []. Several receptor antagonists have been reported [, , , ], although none, so far, have been show to be effective in humans. This entry represents C3a anaphylatoxin chemotactic receptors and C5a anaphylatoxin chemotactic receptor 1/2.
The activation of the complement cascade produces a number of small fragments that are bioactive: potent chemoattractants and secretagogues that act on immune and non-immune cells []. Similar peptides can also be released by the actions of non-complement proteases, for instance during clotting []. Initially these were termed anaphylatoxins because of their effect on mast cell histamine release, but were reclassified as complement component peptides. They include C3a and C5a, which are involved immune response [], neural development and organ regeneration [, ]. A third peptide, C4a, has a similar structure, but it is inactive in humans []. Since the primary function of complement component peptides is in inflammation, they are important targets for the development of anti-inflammatory therapies [].The anaphylatoxin chemotactic receptors (also known as complement peptide receptors) are a group of rhodopsin-like G-protein coupled receptors (GPCRs) [, , , ]. There are three subtypes: C3a anaphylatoxin chemotactic receptor (C3AR1) [], C5a anaphylatoxin chemotactic receptor (C5AR1) []and C5a anaphylatoxin chemotactic receptor C5L2 (C5AR2) []. Both C3AR1 and C5AR1 receptors are classical GPCRs. However, C5AR2 appears to be permanently uncoupled from G proteins but can associate with beta-arrestin []. Nevertheless, it has been shown that activation of both C5AR1 and C5AR2 is required for a full pro-inflammatory response, particularly in mice []. Several receptor antagonists have been reported [, , , ], although none, so far, have been show to be effective in humans. This entry represents C5AR2, also known as complement component 5a receptor 2.
