| First Author | Donnachie E | Year | 2016 |
| Journal | Am J Pathol | Volume | 186 |
| Issue | 5 | Pages | 1221-33 |
| PubMed ID | 26968340 | Mgi Jnum | J:231909 |
| Mgi Id | MGI:5775491 | Doi | 10.1016/j.ajpath.2015.12.019 |
| Citation | Donnachie E, et al. (2016) Trehalose 6,6-Dimycolate from Mycobacterium tuberculosis Induces Hypercoagulation. Am J Pathol 186(5):1221-33 |
| abstractText | Tuberculosis (TB) remains a global health concern. Trehalose 6'6-dimycolate (TDM) activates innate inflammation and likely also stimulates chronic inflammation observed during disease progression. Noninfectious models using purified TDM oil/water emulsions elicit pathologic findings observed in patients with TB. We introduce a new TDM model that promotes inflammatory lung pathologic findings and vascular occlusion and hemorrhage. C57BL/6 and BALB/c mice were injected with 10 mug of i.p. TDM in light mineral oil (TDM-IP). At day 7, another injection of 10 mug of i.v. TDM in oil/water emulsion was given (TDM-IV). The i.p./i.v. TDM (TDM-IVIP) group was compared with mice injected once with i.v. or i.p. TDM. The responses to TDM-IP, TDM-IV, or TDM-IPIV were consistent between mouse strains. Mice that received TDM-IV and TDM-IPIV had inflammatory pathologic findings with increases in inflammatory and T-cell cytokines, and the TDM-IPIV group had further enhancement of IL-10 and granulocyte-macrophage colony-stimulating factor. The TDM-IPIV group had increased CD4(+) T cells in lung tissue, significantly increased coagulation, decreased clot formation time, and increased maximum clot firmness. Masson's trichrome staining revealed increased deposition of collagen in the occluded vasculature. TDM-IPIV promotes a hypercoagulopathy state, independent of inflammation. This new model argues that TDM is sufficient to generate the hypercoagulopathy observed in patients with TB. |
