1. Trehalose 6,6-Dimycolate from Mycobacterium tuberculosis Induces Hypercoagulation.
- Author
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Donnachie E, Fedotova EP, and Hwang SA
- Subjects
- Animals, Antigens, CD metabolism, Collagen metabolism, Cytokines metabolism, Disease Models, Animal, Female, Granulocyte-Macrophage Colony-Stimulating Factor biosynthesis, Immunity, Innate drug effects, Lung blood supply, Lung immunology, Lymphocytes immunology, Macrophages immunology, Mice, Inbred BALB C, Mice, Inbred C57BL, Mycobacterium tuberculosis, Neutrophils immunology, Pneumonia chemically induced, Pneumonia immunology, Pneumonia pathology, Pulmonary Veno-Occlusive Disease chemically induced, Pulmonary Veno-Occlusive Disease immunology, Pulmonary Veno-Occlusive Disease pathology, Thrombelastography methods, Thrombophilia immunology, Thrombophilia pathology, Adjuvants, Immunologic toxicity, Cord Factors toxicity, Thrombophilia chemically induced
- Abstract
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 μg of i.p. TDM in light mineral oil (TDM-IP). At day 7, another injection of 10 μg 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., (Copyright © 2016. Published by Elsevier Inc.)
- Published
- 2016
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