Upregulation of Monocyte Urokinase Plasminogen Activator Receptor during Human Endotoxemia

Abstract

The receptor for urokinase-type plasminogen activator (uPAR) (CD87) plays an important role in leukocyte adhesion and migration. To assess the effect of endotoxin on cellular uPAR, uPAR expression was determined on leukocytes by fluorescence-activated cell sorter analysis in seven healthy subjects following intravenous injection of endotoxin (lot G; 4 ng/kg). Endotoxin induced a transient increase in uPAR expression on monocytes, reaching a 92% ؎ 46% increase over baseline expression after 6 h (P < 0.05). Endotoxin did not influence uPAR expression on granulocytes, while uPAR remained undetectable on lymphocytes. Endotoxin also increased soluble uPAR levels in plasma (P < 0.05). Stimulation of human whole blood with endotoxin or gram-positive stimuli in vitro also resulted in an upregulation of monocyte uPAR expression. Although tumor necrosis factor alpha (TNF) upregulated monocyte uPAR expression, anti-TNF did not influence the endotoxin-induced increase in monocyte uPAR expression. These data suggest that infectious stimuli may influence monocyte function in vivo by enhancing the expression of uPAR.

Borrelia burgdorferiand Other Bacterial Products Induce Expression and Release of the Urokinase Receptor (CD87)

“…In vitro, a number of proinflammatory agents and growth factors such as PMA (23), TGF-␤ and TNF-␣ (24), and nerve growth factor (25) have an enhancing effect on cellular uPAR expression, and uPAR is overexpressed in a number of types of cancerous tumors (26). In the context of infection, LPS in vitro (27,28) and in vivo (29,30), and muramyl dipeptide in vitro (27), can cause an increase in expression of uPAR by monocytes and neoplastic cells. Lyme disease is characterized by inflammatory manifestations in skin, heart, CNS, and joints (2), resulting in tissue damage due to infiltration of inflammatory cells, primarily monocytes/macrophages.…”

Concurrent Upregulation of Urokinase Plasminogen Activator Receptor and CD11b during Tuberculosis and Experimental Endotoxemia

“…Venous blood samples were obtained directly before and 6 h after injection of LPS. (The timing of blood sampling was based on a previous study, in which the effect of intravenous LPS on cellular uPAR expression in humans in vivo was determined [3]). Blood was put on ice immediately, and erythrocytes were lysed with bicarbonate-buffered ammonium chloride solution (pH 7.4).…”

Diagnostic Value of 25-Hydroxyvitamin D Level and New Cytokines in Neonatal Sepsis

“…Kingsmore et al studied more than 100 cytokines in septic premature infants, and found that 6 of them, one of which was uPAR, were statistically higher in the sepsis group (25). Pascale et al showed that bacteria and bacterial products influence monocyte function by exerting a stimulating effect on uPAR expression, and tumor necrosis factor alpha (TNF-a) is capable of increasing uPAR mRNA levels in monocytic cells in experimental human endotoxemia (26). Huttunen et al showed that plasma suPAR level is a sensitive and specific independent prognostic biomarker for diagnosing patients with bacteraemia (27).…”