| First Author | Corken A | Year | 2022 |
| Journal | Radiother Oncol | Volume | 167 |
| Pages | 143-148 | PubMed ID | 34971661 |
| Mgi Jnum | J:339881 | Mgi Id | MGI:7524470 |
| Doi | 10.1016/j.radonc.2021.12.030 | Citation | Corken A, et al. (2022) Platelet glycoprotein Ibalpha provides radiation protection. Radiother Oncol 167:143-148 |
| abstractText | BACKGROUND AND PURPOSE: Platelet membrane glycoprotein Ibalpha (GPIbalpha), the major ligand-binding subunit of the GPIb-IX-V complex, binds to a number of ligands contributing to hemostasis, thrombosis, and inflammation. Binding to von Willebrand factor (VWF) initiates the process of hemostasis/thrombosis, while binding to the leukocyte receptor Macrophage-1 antigen (Mac-1) has been implicated in modulating the inflammatory response. Thus as GPIbalpha resides at the nexus of thrombosis and inflammation, we investigated the impact of GPIbalpha on radiation injury outcomes as this injury triggers both the thrombotic and inflammatory pathways. MATERIALS AND METHODS: We used wild-type (WT) C57BL/6J mice and a dysfunctional GPIbalpha mouse model, in which endogenous GPIbalpha is replaced with a non-functional alpha-subunit (hIL-4R/Ibalpha), to determine whether the impairment of platelet GPIbalpha alters radiation response. Following exposure to 8.5 Gy total body irradiation (TBI), a series of parameters including radiation lethality, platelet-neutrophil/monocyte interactions, neutrophil/monocyte activation, serum cytokine levels and intestinal injury, were compared between the strains. RESULTS: The lack of functional GPIbalpha resulted in higher radiation lethality, greater monocyte activation, increased levels of serum pro-inflammatory cytokines, heightened intestinal damage, and a reduction of intestinal neutrophil recovery. CONCLUSION: These data suggest that loss of platelet GPIbalpha enhances radiation toxicity and that GPIbalpha-mediated interactions may play a crucial role in limiting radiation damage. Thus, a mechanistic understanding of the biological impact of GPIbalpha following TBI could provide crucial insights for improving the safety of radiotherapy and minimizing the deleterious effects of accidental or occupational exposure to high-dose radiation. |
