Characterization of protein C receptor expression in monocytes.
Many sequelae associated with endotoxaemic-induced shock result from excessive production of the cytokine mediators, tumour necrosis factor alpha (TNF-alpha), interleukin 1 (IL-1) and IL-6 from lipopolysaccharide (LPS)-activated 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 anti-inflammatory response is achieved remains unknown; however, the recently described endothelial protein C receptor (EPCR) appears to be essential for this function. The pivotal role that monocytes play in the pathophysiology of septic shock led us to investigate the possible expression of a protein C receptor on the monocyte membrane. We used similarity algorithms to screen human sequence databases for paralogues of the EPCR but found none. However, using reverse transcription-polymerase chain reaction (RT-PCR), we detected an mRNA transcribed in primary human monocytes and THP1 cells that was identical to human EPCR mRNA. We also used immunocytochemical analysis to demonstrate the expression 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 pathway involving primary monocytes. Further characterization will be necessary to compare and contrast its biological properties with those of EPCR.
Galligan
L
L
National Centre for Hereditary Coagulation Disorders, St James's Hospital, Dublin, Ireland.
Livingstone
W
W
Volkov
Y
Y
Hokamp
K
K
Murphy
C
C
Lawler
M
M
Fukudome
K
K
Smith
O
O
D001779:Blood Coagulation Factors; D018076:DNA, Complementary / Q000235:genetics; D030541:Databases, Genetic; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D009000:Monocytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D011956:Receptors, Cell Surface / Q000097:blood* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D001779:Blood Coagulation Factors; D018076:DNA, Complementary; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C091963:activated protein C receptor