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Heparin, a mammalian polysaccharide, is a widely used anticoagulant medicine to treat thrombotic disor ders. It is also known to improve outcomes in sepsis, a leading cause of mortality resulted from infection induced immune dysfunction. Whereas it is relatively clear how heparin exerts its anticoagulant effect, the
immunomodulatory mechanisms enabled by heparin remain enigmatic. Here, we show that heparin pre vented caspase-11-dependent immune responses and lethality in sepsis independent of its anticoagulant properties. Heparin or a chemically modified form of heparin without anticoagulant function inhibited the alar min HMGB1-lipopolysaccharide (LPS) interaction and prevented the macrophage glycocalyx degradation by heparanase. These events blocked the cytosolic delivery of LPS in macrophages and the activation of cas pase-11, a cytosolic LPS receptor that mediates lethality in sepsis. Survival was higher in septic patients
treated with heparin than those without heparin treatment. The identification of this previously unrecognized heparin function establishes a link between innate immune responses and coagulation.[/vc_column_text][vc_column_text]
Hpse-/- mice from GemPharmatech (strain ID, T017525) is used in the study to understand the effects of heparin on cytosolic delivery of LPS.
Find out more about GemPharmatech’s KOAP and their growing repository.
https://doi.org/10.1016/j.immuni.2021.01.007[/vc_column_text][/vc_column][/vc_row][vc_row][vc_column][vc_column_text]
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Shao, F., Liu, Q., Zhu, Y. et al. Targeting chondrocytes for arresting bony fusion in ankylosing spondylitis. Nat Commun 12, 6540 (2021). https://doi.org/10.1038/s41467-021-26750-6
Li, Y., Lu, Y., Lin, SH. et al. Insulin signaling establishes a developmental trajectory of adipose regulatory T cells. Nat Immunol 22, 1175–1185 (2021). https://doi.org/10.1038/s41590-021-01010-3
Bai, L., Zhao, Y., Dong, J. et al. Coinfection with influenza A virus enhances SARS-CoV-2 infectivity. Cell Res 31, 395–403 (2021). https://doi.org/10.1038/s41422-021-00473-1
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