C5a stimulates secretion of tumor necrosis factor from human mononuclear cells in vitro. Comparison with secretion of interleukin 1 beta and interleukin 1 alpha.

Abstract

We have demonstrated that purified C5a is a potent stimulus to human PBMC secretion of TNF-alpha, IL-1 beta, and IL-1 alpha, which proceeds in a dose-dependent fashion. At a given concentration of C5a, TNF-alpha and IL-1 beta secretion did not differ significantly; both were secreted in significantly greater quantity than IL-1 alpha. Clinical conditions such as Gram-positive and Gram-negative bacterial infections, trauma, and immune complex diseases activate complement. Through the mediation of TNF and IL-1 secreted in response to C5a, these diverse disorders can share common features of fever, coagulopathy, acute phase protein production, and disordered metabolism.

Candidate inhibitors of porcine complement

“…The effects of binding of C5a or C5a desArg to their receptors depend on the cell type expressing them. C5a is known to have a range of effects on the innate immune cells in particular neutrophils and macrophages: it is a chemoattractant and enhance expression of adhesion molecules on the cells both of which are important to direct the phagocytes from the blood to the site of infection/injury (80,81); the molecule induce phagocytosis and the consecutive oxidative burst to kill the phagocytized microorganisms (64), and it releases enzymes from intracellular granules as well as induces production and release of cytokines (82)(83)(84). The effect of C5aR binding of C5a is most extensively studied while the role of C5L2 is less well understood, although recent studies have indicated both important pro-and anti-inflammatory effects of the C5L2 receptor (85,86).…”

A Peptide Derived from the Parasite Receptor, Complement C2 Receptor Inhibitor Trispanning, Suppresses Immune Complex-Mediated Inflammation in Mice

“…The anaphylatoxins also regulate inflammatory cytokines. C3a regulates the synthesis of IL-6 and TNF-␣ from B lymphocytes and monocytes (39,40); C5a regulates the synthesis of IL-6 and TNF-␣ from leukocytes (41,42) and triggers the release of C-X-C chemokines such as macrophage inflammatory protein-2 from MCs.…”

Increased concentration of the complement split product C5a in acute pyelonephritis during pregnancy

“…A solid body of evidence indicates that C5a stimulates the white blood cell release of proinflammatory cytokines. In vitro studies have shown that C5a induces the expression of IL-1 [8,47,48] and IL-8 [6] by monocytes. In animal and in vitro studies, C5a augmented LPS-induced release of proinflammatory cytokines such as IL-6 [7] from neutrophils and TNF [8,49] from mononuclear cells.…”

“…In vitro studies have shown that C5a induces the expression of IL-1 [8,47,48] and IL-8 [6] by monocytes. In animal and in vitro studies, C5a augmented LPS-induced release of proinflammatory cytokines such as IL-6 [7] from neutrophils and TNF [8,49] from mononuclear cells. On the other hand, these pro-inflammatory cytokines induced the expression of anaphylatoxins in white blood cells.…”

“…Anaphylatoxins C3a, C4a and C5a are proinflammatory peptides released from the cleavage of their native components following activation of the complement cascade. These molecules induce vascular permeability [2][3][4], smooth muscle contraction [3][4][5], the release of pro-inflammatory cytokines [6][7][8] and white blood cell chemotaxis [9][10][11]. Among anaphylatoxins, C5a is the most potent [4].…”