Abstract 409: CD163-TWEAK Interaction Regulates Tissue Regeneration After Ischemic Injury
Macrophages are an essential component of the response to ischemic injury and direct inflammation and its resolution necessary for proper tissue repair. However, a complete understanding of their exact roles in this process is lacking. CD163, a type I transmembrane glycoprotein, is a receptor for hemoglobin:haptoglobin complexes and is exclusively expressed on macrophages. Its extracellular portion circulates in the blood as a soluble protein of unknown function. Here we show that during hindlimb ischemia, soluble CD163 functions as a decoy receptor for TWEAK (tumor necrosis factor-like weak inducer of apoptosis), a secreted pro-inflammatory cytokine of the tumor necrosis factor family, to regulate TWEAK-induced activation of canonical NF-κB and Notch signaling necessary for myogenic progenitor cell proliferation. Mice with deletion of CD163 demonstrated transiently elevated levels of TWEAK, which activated of both canonical NF-KB and Notch signaling, and muscle satellite cell proliferation and tissue regeneration not limited to the site of injury. Our findings highlight a novel mechanism by which macrophages coordinate systemic tissue repair after ischemic injury through control of the pro-inflammatory cytokine TWEAK.
Author Disclosures: H. Akahori: None. V. Karmali: None. R. Polavarapu: None. A. Lyle: None. D. Weiss: None. E. Shin: None. A. Husain: None. N. Naqvi: None. R.V. Dam: None. A. Habib: None. C.U. Choi: None. A.L. King: None. K. Pachura: None. R. Taylor: None. D.J. Lefer: None. A.F. Virmani: None.
- © 2015 by American Heart Association, Inc.