Sepsis frequently is a complication observed in trauma and burn patients. This patient group often displays hypotensive shock, disseminated intravascular coagulation, and a hypermetabolic state culminating in multiple organ failure and death. Because of the high incidence of gram-negative infections in these patients a critical role for bacterial lipopolysaccharides (LPS) has been suggested and it is generally agreed that LPS is important in initiating the pathophysiologic changes observed in these patients. Unfortunately, there is little known about the release of LPS from bacteria during sepsis in either man or animal models that approximate bacteremia and the subsequent interactions of the released LPS with plasma proteins. On the other hand, there is a great deal of new information about the interactions of highly purified LPS with plasma proteins that has derived from in vitro and in vivo animals studies. The experiments proposed here will attempt to bridge this gap in our knowledge by studying the release of LPS from intact bacteria and bacterial membrane fragments in vitro and in vivo in animal models. These studies will utilize quantitative biochemical and immunologic techniques to study the release of LPS from bacteria and interaction of the released LPS with plasma proteins. A specific emphasis will be placed on further defining the role of the newly recognized acute phase protein, lipopolysaccharide binding protein (LBP), on modulating the interactions of LPS with host plasma proteins and cells. Our long range goal is to apply the information obtained from these studies to better understand the metabolism of LPS in the septic patient.
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