Chemokine CXCL4 interactions with extracellular matrix proteoglycans mediate wide-spread non-receptor mediated immune cell recruitment
Gray, A. L.; Karlsson, R.; Roberts, A. R.; Ridley, A. J.; Pun, N.; Hughes, C.; Medina-Ruiz, L.; Birchenough, H.; Salanga, C.; Yates, E. A.; Turnbull, J. E.; Handel, T. M.; Graham, G.; Jowitt, T. A.; Schiessl, I.; Richter, R. P.; Miller, R. L.; Dyer, D. P.
Show abstract
Leukocyte recruitment from the vasculature into tissues is a crucial component of the immune system, but is also key to inflammatory disease. Chemokines are central to this process but have yet to be therapeutically targeted during inflammation, due to a lack of mechanistic understanding. Specifically, CXCL4 (PF4) has no established receptor that explains its function. Here we use biophysical, in vitro and in vivo techniques to determine the mechanism underlying CXCL4 mediated leukocyte recruitment. We demonstrate that CXCL4 binds to glycosaminoglycan (GAG) sugars within the endothelial extracellular matrix resulting in increased vascular permeability and non-specific recruitment of a range of leukocytes. Furthermore, GAG sulphation confers selectivity onto chemokine localisation. These findings represent a new understanding of chemokine biology, providing novel mechanisms for future therapeutic targeting. One sentence summaryCXCL4 binds to extracellular matrix proteoglycans resulting in increased vascular permeability and recruitment of a wide range of different leukocytes via a non-canonical mechanism.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- The chemorepellent, SLIT2, bolsters innate immunity against Staphylococcus aureus 96%
- Murine Alveolar Macrophages Rapidly Accumulate Intranasally Administered SARS-CoV-2 Spike Protein leading to Neutrophil Recruitment and Damage 96%
- Caveolin-1 protects endothelial cells from extensive expansion of transcellular tunnel by stiffening the plasma membrane 95%
Similar papers in this journal
- Acidosis, Zinc and HMGB1 in Sepsis: A Common Connection Involving Sialoglycan Recognition 94%
- Solution structure and synaptic analyses reveal determinants of bispecific T cell engager potency 94%
- Brain endothelial STING1 activation by Plasmodium-sequestered heme promotes cerebral malaria via type I IFN response. 94%
Similar papers in this journal
- Chemokines form complex signals during inflammation and disease that can be decoded by extracellular matrix proteoglycans 98%
- Functional anatomy of the full length CXCR4-CXCL12 complex systematically dissected by quantitative model-guided mutagenesis 94%
- Specificity and promiscuity of JAK recruitment regulates pleiotropy of cytokine-receptor signaling 93%
Similar papers in this journal
- Opsonization by non-neutralizing antibodies can confer protection to SARS-CoV-2 despite Spike-dependent modulation of phagocytosis 95%
- Extratubular polymerized uromodulin induces leukocyte recruitment and inflammation in vivo 95%
- TNF-a induces VE-cadherin-dependent gap/JAIL cycling through an intermediate state essential for neutrophil transmigration 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.