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Vascular and dendritic cell coagulation signaling in sepsis progression
Author(s) -
RUF W.,
FURLANFREGUIA C.,
NIESSEN F.
Publication year - 2009
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2009.03374.x
Subject(s) - sepsis , signal transduction , sphingosine 1 phosphate receptor , immunology , inflammation , microbiology and biotechnology , cancer research , coagulation , receptor , biology , sphingosine 1 phosphate , medicine , sphingosine
Summary. The intrinsic signaling networks of the coagulation pathways have recently emerged as crucial determinants for survival in sepsis and systemic inflammatory response syndromes. Protease activated receptor (PAR) 1 is central to both lethality promoting and vascular protective signaling. In the vascular anticoagulant pathway, EPCR/aPC‐PAR1 signaling prevents vascular leakage and genetic or acute deficiencies in this pathway promote lethality. In addition, coagulation signaling acts directly on cells of the innate immune system. Dendritic cell (DC) thrombin‐PAR1 signaling is coupled to the migration promoting sphingosine 1 phosphate receptor 3 (S1P3). Thrombin generated in the lymphatic compartment perturbs DCs to promote systemic inflammation and disseminated intravascular coagulation in severe sepsis. Signaling‐selective aPC variants and selective modulators of the S1P receptor system attenuate sepsis lethality, suggesting novel therapeutic approaches that can be employed to rebalance alterations in the coagulation signaling pathways in severe inflammatory disorders.