endotoxin

Endotoxin (LPS) consists of three parts: O antigen (used for serotyping), core polysaccharide, and lipid A, which is the toxic component responsible for its biological effects. Unlike exotoxins, endotoxin is heat-stable, not actively secreted, and part of the bacterial structure itself—it is released when gram-negative bacteria die or their cell wall is disrupted (e.g., by antibiotics or immune attack). Lipid A binds to Toll-like receptor 4 (TLR4) on macrophages and other immune cells, along with CD14 and MD-2 co-receptors, triggering activation of NF-κB and release of pro-inflammatory cytokines such as TNF-α, IL-1, and IL-6. This cascade underlies the clinical manifestations of gram-negative sepsis: fever (via IL-1 and prostaglandins acting on the hypothalamus), hypotension and vascular permeability (septic shock), activation of complement and coagulation cascades leading to DIC, and generalized inflammation. Because it is not a specific protein, endotoxin is a poor vaccine target (unlike exotoxins, which can be converted into toxoids). Clinically important gram-negative organisms with endotoxin include E. coli, Neisseria meningitidis, and Pseudomonas aeruginosa. The Limulus amebocyte lysate (LAL) assay is used to detect endotoxin in the lab. Endotoxin should be distinguished from exotoxins, which are secreted proteins with specific mechanisms (e.g., diphtheria toxin, botulinum toxin) and are typically more potent and antigenic than endotoxin.