uptake and accumulation of oxidized low-density lipoprotein during mycobacterium tuberculosis infection in guinea pigs吸收和积累的氧化低密度脂蛋白在结核分枝杆菌感染在几内亚猪.pdfVIP

Uptake and Accumulation of Oxidized Low-Density Lipoprotein during Mycobacterium tuberculosis Infection in Guinea Pigs ´ ´ Gopinath S. Palanisamy, Natalie M. Kirk, David F. Ackart, Andres Obregon-Henao, Crystal A. Shanley, Ian M. Orme, Randall J. Basaraba* Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, United States of America Abstract The typical host response to infection of humans and some animals by M. tuberculosis is the accumulation of reactive oxygen species generating inflammatory cells into discrete granulomas, which frequently develop central caseous necrosis. ¨ In previous studies we showed that infection of immunologically naıve guinea pigs with M. tuberculosis leads to localized and systemic oxidative stress that results in a significant depletion of serum total antioxidant capacity and the accumulation of malondialdehyde, a bi-product of lipid peroxidation. Here we show that in addition, the generation of excessive reactive oxygen species in vivo resulted in the accumulation of oxidized low density lipoproteins (OxLDL) in pulmonary and extrapulmonary granulomas, serum and lung macrophages collected by bronchoalveolar lavage. Macrophages from ¨ immunologically naıve guinea pigs infected with M. tuberculosis also had increased surface expression of the type 1 scavenger receptors CD36 and LOX1, which facilitate the uptake of oxidized host macromolecules including OxLDL. Vaccination of guinea pigs with Bacillus Calmette Guerin (BCG) prior to aerosol chal