Fig. 6
Nitric Oxide Is Necessary for Early Demyelination (A) Representative confocal images of a macrophage aggregate in the spinal cord of an mpeg1 larva infected with M. leprae and stained with α-iNOS antibody. Scale bar, 10 μm. (B) Mean percentage of infected mpeg1-positive macrophages that also express iNOS in 7 dpf larvae 5 dpi with WT M. marinum or M. marinum:PGL-1. (Student’s t test.) (C) Mean percentage of infected mpeg1-positive macrophages that stain with α-nitrotyrosine antibody (nitroT) in larvae like in (B). (Student’s t test). (D) Mean number of myelin protrusions per animal in 5 dpf mbp larvae 2 dpi with M. leprae, which were treated with 0.5% DMSO vehicle (-), iNOS inhibitor (L-NAME), or ROS/RNS scavenger (cPTIO). (∗∗p < 0.01; ∗∗∗p < 0.001; one-way ANOVA with Dunnett’s multiple comparison test.) (E) Mean number of myelin protrusions per animal in 5 dpf mbp larvae 2 dpi with M. marinum:PGL-1, treated like in (D). (∗p < 0.05; ∗∗p < 0.01; one-way ANOVA with Dunnett’s multiple comparison test.) (F) Mean number of myelin protrusions per animal in 5 dpf mbp larvae 2 dpi with M. marinum:PGL-1, which were treated with 0.5% DMSO vehicle (“-”), nitric oxide scavenger (cPTIO), or ROS scavenger NAC. (∗p<0.05; ∗∗∗p<0.001; one-way ANOVA with Dunnett’s multiple comparison test.) (G) Mean number of myelin protrusions per animal in larvae infected like in (F), which were soaked post-injection in 0.5% DMSO vehicle (“-”) or in nitric oxide donors SNAP or spermine NONOate (spNO). (∗p<0.05; ∗∗∗p<0.001; one-way ANOVA with Dunnett’s multiple comparison test.) See also Figure S5. |
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Reprinted from Cell, 170, Madigan, C.A., Cambier, C.J., Kelly-Scumpia, K.M., Scumpia, P.O., Cheng, T.Y., Zailaa, J., Bloom, B.R., Moody, D.B., Smale, S.T., Sagasti, A., Modlin, R.L., Ramakrishnan, L., A Macrophage Response to Mycobacterium leprae Phenolic Glycolipid Initiates Nerve Damage in Leprosy, 973-985.e10, Copyright (2017) with permission from Elsevier. Full text @ Cell