Souza Cleverson D, Evanson Oral A, Weiss Douglas J
Department of Veterinary Science, University of Minnesota, St. Paul, MN 55108, USA.
Microbes Infect. 2007 Nov-Dec;9(14-15):1545-52. doi: 10.1016/j.micinf.2007.08.008. Epub 2007 Sep 2.
We compared the kinetics of activation and antimicrobial activities of MAPK-p38 and MAPK-ERK in bovine monocytes infected with Mycobacterium avium subsp. paratuberculosis (MAP) and Mycobacterium avium subsp. avium (Maa). Monocytes were incubated with MAP or Maa organisms with or without a specific inhibitor of the MAPK-p38 pathway (SB203580), and MAPK phosphorylation and antimicrobial functions of monocytes were evaluated. At early time points MAPK-p38 phosphorylation was greater in MAP-infected bovine monocytes than in Maa-infected monocytes. At later time points MAPK-p38 phosphorylation by both organisms was similar. MAPKp38 phosphorylation in MAP-infected monocytes was similar to negative control cells, whereas in Maa-infected this activation remained greater than negative control cells. Increase phosphorylation MAPK-ERK was similar at all time points for both organisms. Bovine monocytes had minimal capacity to kill MAP organisms, to acidify MAP-containing phagosomes, or to form phagolysosome. Alternatively, bovine monocytes were able to kill Maa organisms. Addition of SB203580 to monocyte cultures increased phagosome acidification, phagolysosome formation, and killing of MAP and Maa organisms. Taken together these data indicate that early transient activation of MAPK-p38 in bovine mononuclear phagocytes by MAP organisms may be a key mechanism involved in the capacity of MAP to survive in bovine monocytes.
我们比较了感染副结核分枝杆菌（MAP）和鸟分枝杆菌亚种（Maa）的牛单核细胞中丝裂原活化蛋白激酶p38（MAPK-p38）和丝裂原活化蛋白激酶细胞外信号调节激酶（MAPK-ERK）的激活动力学及抗菌活性。将单核细胞与MAP或Maa菌一起孵育，同时添加或不添加MAPK-p38途径的特异性抑制剂（SB203580），然后评估单核细胞的MAPK磷酸化和抗菌功能。在早期时间点，感染MAP的牛单核细胞中MAPK-p38的磷酸化程度高于感染Maa的单核细胞。在后期时间点，两种菌引起的MAPK-p38磷酸化相似。感染MAP的单核细胞中MAPKp38的磷酸化与阴性对照细胞相似，而在感染Maa的单核细胞中，这种激活仍高于阴性对照细胞。两种菌在所有时间点MAPK-ERK的磷酸化增加情况相似。牛单核细胞杀灭MAP菌、酸化含MAP的吞噬体或形成吞噬溶酶体的能力极低。相反，牛单核细胞能够杀灭Maa菌。向单核细胞培养物中添加SB203580可增加吞噬体酸化、吞噬溶酶体形成以及对MAP和Maa菌的杀灭。综上所述，这些数据表明MAP菌在牛单核吞噬细胞中早期短暂激活MAPK-p38可能是MAP在牛单核细胞中存活能力的关键机制。
