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Title: MECHANISMS OF BACTERIAL LIPOPOLYSACCHARIDE-INDUCED ENDOTHELIEL APOPTOSIS

Author
item Bannerman, Douglas
item GOLDBLUM, SIMEON - U MD BALTIMORE

Submitted to: American Journal of Physiology - Lung Cellular and Molecular Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/11/2002
Publication Date: 6/1/2003
Citation: BANNERMAN, D.D., GOLDBLUM, S.E. MECHANISMS OF BACTERIAL LIPOPOLYSACCHARIDE-INDUCED ENDOTHELIEL APOPTOSIS. AMERICAN JOURNAL OF PHYSIOLOGY LUNG CELLULAR AND MOLECULAR PHYSIOLOGY. vol. 284, pp. 899-914, 2003.

Interpretive Summary: The major cause of mastitis is bacterial infection. Approximately 50% of all of these infections are caused by Gram-negative bacteria. A common denominator of Gram-negative bacteria is the presence of a highly pro-inflammatory molecule, lipopolysaccharide (LPS), on the outer membrane of these bacteria. In addition to the ability of LPS to activate the immune system, LPS has been shown to injure host tissue both in humans and in cows. Further, Gram-negative infections have been shown to induce the death of milk producing epithelial cells in the mammary gland. Scientists in the Immunology and Disease Resistance Laboratory at the USDA in Beltsville, Maryland, are investigating the role that cell death (also known as "apoptosis") plays in the development and outcome of mastitis. Recent findings have elucidated the mechanism by which the Gram-negative bacterial constituent, LPS, nduces apoptosis. These findings are detailed in the present manuscript. Further areas of investigation will consider the ability of agents that inhibit cell death to be used as potential therapeutics in the setting of mastitis and systemic infection.

Technical Abstract: Gram-negative bacterial sepsis remains a common, life-threatening event. The prognosis for patients who develop sepsis-related complications including the development of the adult respiratory distress syndrome (ARDS) remains poor. A common finding among patients and experimental animals with sepsis and ARDS is endothelial injury and/or dysfunction. A component of the outer membrane of Gram-negative bacteria, lipopolysaccharide (LPS) or endotoxin, has been implicated in the pathogenesis of much of the endothelial cell injury and/or dysfunction associated with these disease states. LPS is a highly pro-inflammatory molecule that elicits a wide array of endothelial responses, including the upregulation of cytokines, adhesion molecules, and tissue factor. In addition to activation, LPS induces endothelial cell death that is apoptotic in nature. This review will summarize the evidence for LPS-induced vascular endothelial injury and examine the molecular signaling pathways that activate and inhibit LPS-induced endothelial apoptosis. Further, the role of apoptotic signaling molecules in mediating LPS-induced activation of endothelial cells will be considered.