Characterization of protein C receptor expression in monocytes

L Galligan, W Livingstone, Y Volkov, K Hokamp, C Murphy, M Lawler, K Fukudome, O Smith, Mark Lawler

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)408-14
Number of pages7
JournalBritish Journal of Haematology
Volume115
Issue number2
Publication statusPublished - Nov 2001

Keywords

  • Blood Coagulation Factors
  • DNA, Complementary
  • Databases, Genetic
  • Fluorescent Antibody Technique, Indirect
  • Humans
  • Monocytes
  • RNA, Messenger
  • Receptors, Cell Surface
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured

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