International Union of Basic and Clinical Pharmacology. LXXXVII. Complement Peptide C5a, C4a, and C3a Receptors

Is the Complement Activation Product C3a a Proinflammatory Molecule? Re-evaluating the Evidence and the Myth

“…In the acute setting, C3a prevents mobilization of neutrophils, limits their accumulation into tissues, and, therefore, reduces the inflammatory response at the tissue level. However, in certain chronic disease models, such as asthma and rheumatoid arthritis, C3a clearly demonstrates certain proinflammatory actions and contributes to disease progression (8). The difference in the response of inflamed tissues to C3a, between the acute and chronic phases of inflammation, may well be due to the differing cell types involved (e.g., neutrophils versus monocyte/ macrophages; Fig.…”

“…Additionally, at the site of acute inflammation, carboxypeptidases preferentially degrade C5a over C3a, perhaps allowing for C3a to escape degradation and exert systemic actions (8). We recently showed that one function of this C3a release is to attenuate the neutrophilia associated with injury by confining unmobilized neutrophils to the bone marrow reservoir (32).…”

Smoke Exposure Causes Endoplasmic Reticulum Stress and Lipid Accumulation in Retinal Pigment Epithelium through Oxidative Stress and Complement Activation

“…In both mouse and human there is a single receptor for C3a (C3a-receptor), which can also serve to mediate signaling for C3a desArg. Ligand binding and signaling by the C3a-receptor has been well characterized, a process that involves pertussis toxin-sensitive G␣ i signaling (73). Receptor signaling through the anaphylatoxin receptors can result in changes in intracellular signaling calcium levels, trigger prolonged activation of protein phosphorylation such as ERK1/2 and Akt, and may also involve arrestin binding to the phosphorylated receptor.…”

Mannose-Binding Lectin Promotes Local Microvascular Thrombosis After Transient Brain Ischemia in Mice

“…4 Complement can be activated through the classical, alternative, and lectin pathways that all culminate in the formation of a lytic pore in cell membranes, known as the membrane attack complex, and the production of proinflammatory small protein fragments called anaphylotoxins C3a, C5a, and C4a. 5 Blockade of C3a [6][7][8] and C5a 8,9 receptors is protective against ischemia/reperfusion in animals.…”