Erratum to “Key structures of bacterial peptidoglycan and lipopolysaccharide triggering the innate immune system of higher animals: Chemical synthesis and functional studies”

Abstract

Chemistry-based investigation is reviewed which led to identication of the active entities responsible for the immunostimulating potencies of peptidoglycan and lipopolysaccharide. Though these glycoconjugates which ubiquitously occur in wide range of bacteria as the essential components of their cell envelopes have long been known to enhance the immunological responses of higher animals, neither the precise chemical structures required nor the mechanism of their action had been elucidated until early 1970s. Chemical synthesis of partial structures of peptidoglycan proved N-acetylmuramyl-L-alanyl-D-isoglutamine to be the minimum structure responsible for the activity and led to later identication of its receptor protein Nod2 present in animal cells. Another active partial structure of peptidoglycan, g-D-glutamylmeso-diaminopimelic acid, and its receptor Nod1 were also identied as well. With regard to lipopolysaccharide, its glycolipid part named lipid A was puried and the structure studied. Chemically synthesized lipid A according to the newly elucidated structure exhibited full activity described for lipopolysaccharide known as endotoxin. Synthetic homogeneous lipid A and its structural analogues and labeled derivatives enabled precise studies of their interaction with receptor proteins and the mechanism of their action. Chemical synthesis of homogeneous partial structures of peptidoglycan and lipopolysaccharide gave unequivocal evidences for the concept that denite small molecular parts of these complex macromolecular bacterial glycoconjugates are specically recognized by their respective receptors and trigger our defense system now widely recognized as innate immunity.

Recent Advances in Lipopolysaccharide Recognition Systems

“…Furthermore, soluble lipid A demonstrated the properties of intact LPS, i.e., lethal toxicity and pyrogenicity induced by lipid A was comparable to their corresponding parent LPS. Furthermore, chemically synthesized E. coli lipid A has demonstrated identical endotoxic activities as natural free lipid A, further supporting lipid A as the endotoxic center of LPS [19,25,26].…”

“…Lipid A as well as the polysaccharide regions are able to induce potent immune responses [16,[19][20][21][22]. The lipid A component, independent of the polysaccharide portion, is responsible for various pathophysiological effects including toxicity, mitogenicity, complement reactivity [23,24], and Limulus lysate gelation [7,25,26]. Galanos et al [25] demonstrated that solubilized lipid A administered to mice and rabbits induced toxicity and pyrogenicity.…”