ABSTRACT
Discrepancies in the literature were first directly addressed by McGhee et al., where issues of lipopolysaccharide (LPS) dosage, the potential contribution of background genes unrelated to Lps, and assay sensitivity are discussed in this chapter. Based on glucose utilization and nitric oxide production by LPS-stimulated macrophages and LPS-induced spleen cell mitogenesis, the suggests that this discrepancy might be explained if this strain had been classified prior to its stabilization or if it mutated to a hyporesponsive phenotype within the past 20 years. Platelet-activating factor is a potent LPS-inducible, proinflammatory mediator that has been implicated in endotoxicity and sepsis. Ceramide is a lipid messenger that is principally generated by the hydrolysis of membrane sphingomyelin by sphingomyelinases. Because of its lipid nature, the interaction of ceramide with specific signaling pathways is strictly membrane associated. The formal demonstration that a candidate gene and Lps are allelic may necessitate the conversion of the defective LPS phenotype to the normal phenotype by transfer of specific cloned DNA sequences.
