ABSTRACT. Cellular activation and functional cell surface markers were evaluated during experimentally-induced endotoxemia in healthy horses. Eight healthy adult horses were infused a low dose of endotoxin (lipopolysaccharide from Escherichia coli O26: B6, 30 ng/kg of body weight, IV) and five control horses were given an equivalent volume of sterile saline solution. Venous blood samples were collected for flow cytometric analysis of peripheral blood mononuclear cells (PBMCs) and to measure plasma endotoxin concentrations. Clinical signs of endotoxemia were recorded at 10, 20, 30, 40, 50 min, 1, 2, 3, 4, 8, 16, 24 and 48 hr after endotoxin or saline solution administration. Clinical findings characteristic of endotoxemia (tachycardia, tachypnea, increased rectal temperature, and leukopenia) occurred transiently in all horses administered endotoxin; however, plasma endotoxin concentrations were detectable in only 50% (4/8) of the endotoxin-infused horses. Endotoxin (lipopolysaccharide; LPS) has been shown to play a central role in the pathogenesis of severe sepsis and septic shock accompanied with systemic inflammatory response syndrome (SIRS) caused by gram-negative bacteria [2,9]. In horses with gastrointestinal disorders, endotoxemia is major cause of morbidity and mortality associated with septic shock [18]. Inflammatory mediators such interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-α are increased in horses with endotoxemia [5,28,36]. Many important equine diseases are associated with endotoxemia, thus elucidating important mechanisms in the pathogenesis of this condition in horse could lead to improved treatment.The monocyte is a pivotal cell in mediating the body's response to endotoxemia. Monocytes express CD14, a cell surface receptor that binds complexes formed between LPS and a plasma LPS-binding protein (LBP) [38]. CD14 is a glycosyl-phosphatidyl-inositol (GPI) anchored membrane protein that is expressed on mature monocytes [15]. Moreover, CD14 was identified as a monocyte differentiation marker expressed on the surface of macrophages, neutrophils, and other cells of myeloid linkage [33]. It functions as a co-receptor for bacterial LPS and triggers the induction of inflammatory responses. Recently it has been demonstrated that Toll-like receptor (TLR) 4 may be the predominant cell surface molecule mediating the response to LPS [1,7,20] and the binding of LPS to the CD14-TLR4 complex is effective in generating a functional cellular response [7,20]. CD14 initiates the activation of macrophages for the synthesis of proinflammatory cytokines [13] that stimulate both proliferation and differentiation of CD4 + cell for helper T cell, CD5 + cell specific for peripheral B1-a cell, and CD8 + cell for suppressor and cytotoxic T cell and IgM + cell for B cell. The LPS, an outer-membrane component of gram-negative bacteria, is recognized as one of major causes of septic shock [8]. Downregulation of CD14 has been reported in circulating monocytes of human septic patient [8,14,21,22]. A continuous decrea...