Neutrophil-Derived MMP-8 Drives AMPK-Dependent Matrix Destruction in Human Pulmonary Tuberculosis (original) (raw)
Fig 4
Induced sputum samples of pulmonary TB patients have increased collagenase activity due to neutrophil-derived MMP-8.
(A and B) Induced sputum MPO and NGAL was analyzed by ELISA from n = 51 TB patients and n = 57 healthy controls. MPO and NGAL were increased in patients with pulmonary TB. (C and D) Induced sputum MMP-8 closely correlated with both MPO and NGAL in TB patients, performed using Spearman’s correlation coefficient. (E) Induced sputum collagenase activity is increased in TB patients. (n = 11 each group). Subsets analyzed were representative of the whole cohort analyzed by Mann-Whitney test. (F) Confocal microscopy shows increased DQ collagen degradation in induced sputum of TB patient relative to control. Image is representative of n = 3 each group. Scale bars represent 50μm. (G) Induced sputum MMP-8 and collagenase activity correlate, analyzed by Spearman’s correlation coefficient (n = 22). (H) MMP-8 neutralization suppresses induced sputum collagenase activity from TB patients. MMP-8 neutralizing antibody was added to activated induced sputum with Type I DQ collagen (n = 11). Box and whiskers represent 10–90th percentile with comparison using Wilcoxon-Sign rank test. (I) Induced sputum MMP-8 were higher in patients with pulmonary cavities than those without. * P< 0.05, **P<0.01, ****P<0.0001.