dc.contributor.author | Cox, Katherine J. | |
dc.contributor.author | Chancellor, Matthew | |
dc.contributor.author | Chen, R. | |
dc.contributor.author | McMullen, M. | |
dc.contributor.author | Nagy, L. E. | |
dc.contributor.author | McIntyre, T. M. | |
dc.date.accessioned | 2023-11-02T20:44:14Z | |
dc.date.available | 2023-11-02T20:44:14Z | |
dc.date.issued | 2023-02-17 | |
dc.identifier | ouhd_Cox_murineethanolingestionpromotes_2023 | |
dc.identifier.citation | Cox, K. J., Chancellor, M., Chen, R., McMullen, M., Nagy, L. E., and McIntyre, T. M. (2023, February 17). Murine ethanol ingestion promotes hepatic platelet accumulation mimicking acute Ccl₄ exposure. Poster presented at Research Week, Oklahoma State University Center for Health Sciences, Tulsa, Ok. | |
dc.identifier.uri | https://hdl.handle.net/11244/339888 | |
dc.description.abstract | Background: Dysregulated coagulation contributes to inflammation and fibrosis from chemical injury. Platelets are key contributors to inflammation and are primary sources of TGF-b, PDGF, and EGF that promote fibrosis, and so may contribute to hepatic fibrosis. We questioned whether platelets accumulate during chronic ethanol- or chemical-induced hepatic injury, whether platelet accumulation would occur prior to induction of hepatic fibrotic responses, and whether platelet accumulation reflects deposition of intravascular microthrombi or individual platelets intercalated into liver parenchyma. | |
dc.description.abstract | Methods: We modeled acute hepatic injury with a single injection of CCl₄, a chronic model of moderate ethanol ingestion, or a combination of the two insults. C57Bl6 mice ingested a control liquid diet or provided free access to 1% ethanol (2d), then 2% ethanol (2d, 11% calories). At day 4, mice received, or not, a single i.p. injection of CCl₄ (1 μl/g, 1:3 in olive oil), with sacrifice 72h later. Formalin-fixed livers were transversely sectioned, paraffin-embedded prior to immunohistochemistry with anti platelet integrin gpIIb (CD41), endothelial CD31, or a-smooth muscle actin (aSMA) antibodies with DAPI nuclear staining. Adherent platelets spread to micron thickness, so detection was by serial tyramide amplification (Biotium). This catalyzed reporter deposition system uses a single tyramide dye activated by HRP-derived H₂O₂ to a reactive specie that multiply ligates adjacent molecules before the antibody complex is thermally stripped prior to a subsequent tyramide labeling. | |
dc.description.abstract | Results: Our preliminary data show basal parenchymal platelet deposition with inflammation 24h after CCl₄ injection massively increasing platelet accumulation, with enhanced expression of aSMA, just below the outer Glisson’s sheath encasement, correlating to the area of highest arterial flow (DOI 10.1139/y93- 018). Platelet accumulation, but not aSMA, within liver parenchyma was modestly increased at this time. 72h after CCl₄ injection, subsurface platelet accumulation in association with endothelial cell PECAM1 remained apparent, with aSMA now extended in disordered filaments surrounding portal tracts. Ethanol ingestion alone, similar to CCl₄ exposure, revealed massive platelet accumulation just below the Glisson’s sheath liver encasement in association with endothelial cell PECAM1 without aSMA deposition. The combination of ethanol and CCl₄ presented similarly. | |
dc.description.abstract | Conclusions: We conclude ethanol ingestion promotes hepatic platelet accumulation, providing a nontranscriptional source of fibrotic growth factors, that parallels hepatic injury invoked by CCl₄ exposure. | |
dc.format | application/pdf | |
dc.language | en_US | |
dc.publisher | Oklahoma State University Center for Health Sciences | |
dc.rights | The author(s) retain the copyright or have the right to deposit the item giving the Oklahoma State University Library a limited, non-exclusive right to share this material in its institutional repository. Contact Digital Resources and Discovery Services at lib-dls@okstate.edu or 405-744-9161 for the permission policy on the use, reproduction or distribution of this material. | |
dc.title | Murine ethanol ingestion promotes hepatic platelet accumulation mimicking acute Ccl₄ exposure | |
osu.filename | ouhd_Cox_murineethanolingestionpromotes_2023.pdf | |
dc.type.genre | Presentation | |
dc.type.material | Text | |
dc.subject.keywords | ethanol | |
dc.subject.keywords | hepatic | |
dc.subject.keywords | fibrosis | |