Fibrin complement receptor 3 signaling pathway (WP4136)
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. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP4136 CPTAC Assay Portal]
AuthorsKristina Hanspers , Andrew Mendiola , Katerina Akassoglou , Egon Willighagen , Alex Pico , Eric Weitz , and Martina Summer-Kutmon
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- Investigating the Molecular Processes behind the Cell-Specific Toxicity Response to Titanium Dioxide Nanobelts (2021).
- LMWF5A suppresses cytokine release by modulating select inflammatory transcription factor activity in stimulated PBMC (2020).
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Pathway Ontologycoagulation cascade pathway classical complement pathway inflammatory response pathway
Cell Type Ontologymacrophage microglial cell
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