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<Pathway xmlns="http://pathvisio.org/GPML/2013a" Name="Fibrin complement receptor 3 signaling pathway" Data-Source="WikiPathways" Version="WP5128_r142560" Author="[Khanspers, Egonw]" Last-Modified="20260322091620" Organism="Mus musculus">
  <Comment Source="WikiPathways-description">The blood protein fibrinogen, a key component of the coagulation cascade, has been identified as an early molecular factor triggering inflammation in the brain and periphery (see bibliography). Upon fibrinogen extravasation across leaky vessels (i.e., break down of the blood-brain barrier), fibrinogen is converted by thrombin to insoluble fibrin. Based on published studies, this signaling pathway highlights fibrin as a CD11b/CD18 (complement receptor; CR3) integrin receptor ligand that regulates innate immunity. Fibrin activates central nervous system (CNS) resident microglia and peripheral (bone marrow-derived) macrophages via CR3, leading to intracellular kinase signaling activation including PI3K, AKT1, and RhoA activity that regulates phagocytosis; and NF-κB translocation to the nucleus that transcriptionally regulates proinflammatory cytokines and chemokines that recruit T-cells and macrophages. Canonical LPS-TLR4 activation of innate immune cells and potential mechanisms of CD11b transactivation are shown.


This pathway has been converted from human to mouse from https://www.wikipathways.org/index.php/Pathway:WP4136.</Comment>
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      <bp:YEAR rdf:datatype="http://www.w3.org/2001/XMLSchema#string">2007</bp:YEAR>
      <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Adams RA</bp:AUTHORS>
      <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Bauer J</bp:AUTHORS>
      <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Flick MJ</bp:AUTHORS>
      <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Sikorski SL</bp:AUTHORS>
      <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Nuriel T</bp:AUTHORS>
      <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Lassmann H</bp:AUTHORS>
      <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Degen JL</bp:AUTHORS>
      <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Akassoglou K</bp:AUTHORS>
    </bp:PublicationXref>
  </Biopax>
</Pathway>

