Defective responses to lipid A in C3H/HeJ mice: approaches to an understanding of lipid A-cell interaction.

C3H/HeJ mice have diminished responses to lipopolysaccharide (lipid A) that are due to a mutation in a gene located on chromosome 4. Studies employing this strain o mice have contributed significantly to our understanding of cellular interactions, mediators, and the genetic control involved in various host responses to lipid A. The present review emphasizes areas of research that require further elucidation, such as binding versus triggering sites for lipid A and the state of differentiation of the responding cells that is required for activation by lipid A. Certain experimental approaches to the investigation of the mechanisms of interaction of lipid A with target cells are suggested. Insertion of membrane fragments obtained from lipid A-sensitive cells into nonresponder cells has focused attention on the cell membrane as the primary target for lipid A. Thus, a clearer definition of either binding or triggering sites for lipid A could be gained by employing monoclonal antibodies to specific cell-surface components.