Lipopolysaccharide/lipid A receptors on lymphocytes and macrophages

Significant advances have been realized during the past five years in the understanding of the mechanism(s) by which endotoxic LPS interactions with mammalian lymphoreticular cells leads to characteristic cellular responses. There is now strong experimental evidence to support the concept that specific receptors for the lipid A component of LPS do, in fact, exist and are functional on these cells. While the available data do not rule out a potential contribution of nonspecific hydrophobic interactions of lipid A with the membrane bilayer in the cellular activation process, it would appear that interaction with the LPS receptor alone is sufficient to initiate triggering. Whether there exist more than one molecular entity which might function on mammalian cell membranes as a specific receptor for LPS, or whether different cell types may manifest different LPS receptors remains as an interesting area for future research. Further, the concept that molecular complexes of LPS with mammalian host proteins, such as the acute phase LPS binding protein, might trigger additional novel pathways for cell activation is both exciting and of potential importance. The precise mechanism or mechanisms by which LPS-receptor ligand interactions translate into appropriate transmembrane signalling events is currently uncertain. Clearly there exists evidence for contribution of many of the traditional second signals, although at present, the data are incomplete and not always consistent between laboratories. Of potential concern in this respect are the sometimes rather striking differences noted between lipid A and intact polysaccharide containing S-LPS. While such differences may be significant and important, it should be remembered that S-LPS itself is a potent stimulus for many lymphoreticular cell subpopulations, and any postulated pathways must encompass S-LPS as well as lipid A. In any case, it is likely that the further molecular-biochemical characterization of LPS receptors will yield crucial information for the eventual elucidation of the precise pathways for LPS transmembrane signalling. Such information will be invaluable in the future harnessing of the immunostimulatory potential of LPS as well as the abrogation of its profound deleterious pathophysiological effects in endotoxin shock.