Complement activation by whole endotoxin is blocked by a monoclonal antibody to factor B

Abstract

Sepsis is both a common and, despite present-day therapy, a serious disease. The pathophysiology of the septic response is a complex, multifactorial phenomenon which in part involves the activation of complement by bacterial endotoxin. A monoclonal antibody to human complement factor B, code-named lH5, which was capable of specifically inhibiting the alternative pathway of complement activation at concentrations as low as 1 ,ug/ml, is described. This agent had no effect on the classical pathway of complement activation. It was capable of preventing the activation of complement by even high concentrations (0.1 mg/ml) of whole endotoxin; however, it was ineffective in preventing activation of complement by endotoxin derived from a * Corresponding author. Mailing address: Rush-Presbyterian-St.

The Endotoxin Hypothesis of Parkinson's Disease

“…29,30 Endotoxin can also bind multiple scavenger receptors, activate complement via the alternative pathway, and directly activate complement receptor 3, which may contribute to the neurotoxicity. [31][32][33] Different bacteria can have different variants of LPS with varying capacities to induce inflammation and toxicity. 10 The lipid A component of LPS is sufficient to activate inflammation, but if the number of acyl chains on lipid A is reduced from 6 to 5 or 4, then its ability to activate TLR4 is greatly reduced.…”

“…In some cases, this may also cause cell death by pyroptosis, due to caspase‐1 or caspase‐11 cleaving and activating gasdermin D that permeabilizes the plasma membrane 29,30 . Endotoxin can also bind multiple scavenger receptors, activate complement via the alternative pathway, and directly activate complement receptor 3, which may contribute to the neurotoxicity 31‐33 …”

“… 29 , 30 Endotoxin can also bind multiple scavenger receptors, activate complement via the alternative pathway, and directly activate complement receptor 3, which may contribute to the neurotoxicity. 31 , 32 , 33 …”

Characterization of IFN-γ regulation of the complement factor B gene in macrophages

“…Second, previous analysis of the Bf promoter, primarily in HepG2 cells and murine L cells, has revealed both IFN‐γ and IL‐1‐responsive regions within 400 bases of the transcription initiation site of the Bf gene, but these studies have fallen short of a detailed analysis of these regions 25, 27. Finally, Bf plays an important role in activation of the alternative pathway of complement in sepsis 28. Since the macrophage is an important source of extrahepatic Bf induction, we sought to detail IFN‐γ‐stimulated Bf promoter regulation in the macrophage.…”