Endotoxins

The majority of bacterial toxins are proteins released by bacteria in the medium and are termed exotoxins. However, many gram-negative bacteria, upon lysis or during division, release toxic lipid components of the outer membrane, which are therefore named endotoxins. These molecules are lipopolysaccharides (LPS) of a complex and variable nature that are capable of inducing a variety of local and systemic effects, including fever and toxic shock (1). LPS binds directly to the CD11/CD18 molecules and 95-kDa scavenger receptor of macrophages(3). After fixation to a plasma protein LBP, the complex LPS-LBP is capable of binding the CD14 molecule present on macrophages, neutrophils, and platelets (2). Such binding triggers a variety of effects. Platelets release prostaglandin E₂, tromboxane A ₂, and PAF (platelet-activating factor), and these mediators induce platelet aggregation and coagulation and trombotic phenomena. Activated macrophages and neutrophils release oxygen radicals and nitric oxide, which causes the relaxation of smooth muscles. LPS are the most potent inducer of the release of cytokines from macrophages. It appears that such platelet and inflammatory cells responses have developed in order to respond rapidly to the presence of potentially pathogenic bacteria (3). However, such a defensive response may turn easily into harmful, even deadly, systemic effects when larger amount of LPS are released or bacteria multiply in the blood and release LPS in a tissue so rich in target cells.