Characterization of protein C receptor expression in monocytes

Many sequelae associated with endotoxaemic-induced shock result from excess ive production of the cytokine mediators. tumour necrosis factor alpha (TNF -alpha), interleukin 1 (IL-1) and IL-6 from lipopolysaccharide (LPS)activat ed monocytes. Protein C (PC)/activated protein C (APC) has potent cytokine- modifying properties and is protective in animal models and human clinical trials of sepsis. The precise mechanism by which this antiinflammatory resp onse is achieved remains unknown: however. the recently described endotheli al protein C receptor (EPCR) appears to be essential for this function. The pivotal role that monocytes play in the pathophysiology of septic shock le d us to investigate the possible expression of a protein C receptor on the monocyte membrane. We used similarity algorithms to screen human sequence d atabases for paralogues of the EPCR but found none. However. using reverse transcription-polymerase chain reaction (RT-PCR), we detected an mRNA trans cribed in primary human monocytes and THP1 cells that was identical to huma n EPCR mRNA. We also used immunocytochemical analysis to demonstrate the ex pression of a protein C receptor on the surface of monocytes encoded by the same gene as EPCR. These results confirm a new member of the protein C pat hway involving primary monocytes. Further characterization will be necessar y to compare and contrast its biological properties with those of EPCR.