Matrix metalloproteinase-9 in bronchiolitis obliterans syndrome after lung transplantation

Abstract

Bronchiolitis obliterans syndrome (BOS) is a severe complication after lung transplantation (LTX).In a retrospective cohort study 12 stable healthy recipients (non-BOS) and eight patients with BOS were enrolled after LTX and matrix metalloproteinases (MMP)-9, TIMP-1 and cell characteristics in bronchoalveolar lavage (BAL) samples (n5145) were analysed. BALs from patients with BOS were further divided according to whether they were obtained before (pre-BOS) or after manifestation of BOS (BOS group).The MMP-9/TIMP-1 ratio was significantly increased in the BOS group compared with non-BOS or pre-BOS; furthermore, the ratio was negatively correlated with forced expiratory volume in one second. In zymography, the active form of MMP-9 was detected predominantly in the BOS group. In addition, zymography showed the banding pattern of neutrophil-derived MMP-9, indicating that polymorphonuclear neutrophils (PMNs) were the main source of MMP-9. According to that, MMP-9 was significantly correlated with the number of PMN. In immunocytochemistry, MMP-9 was also associated predominantly with PMN. This is the first study to evaluate the expression of matrix metalloproteinase-9 and tissue inhibitors of metalloproteinases-1 over time during manifestation of a fibroproliferative lung disease in patients. It demonstrates development of bronchiolitis obliterans syndrome after lung transplantation is associated with an imbalance of matrix metalloproteinases-9/tissue inhibitors of metalloproteinase-1 ratio.

Induction of IL-10 Suppressors in Lung Transplant Patients by CD4+25+ Regulatory T Cells through CTLA-4 Signaling

“…Matrix metalloproteinases (MMP) 2 and 9 are capable of cleaving collagen molecules (38). The activity of MMP-2 and MMP-9 has been shown to be up-regulated after lung transplantation (39,40). Also, col-V can be detected in the bronchoalveolar lavage fluid from rat lung allograft recipients but not in normal hosts (14), and col-V-reactive T cells are present in rat lung allografts undergoing rejection.…”

Allograft Airway Fibrosis in the Pulmonary Milieu: A Disorder of Tissue Remodeling

“…The role of MMP-9 in the initiation of fibrosis has been demonstrated in a mouse model of OB (21). Furthermore, in patients with OB, a high ratio of MMP-9 to TIMP-1 has been detected in sputum (31) and bronchoalveolar lavage fluid (32). Since MMP-3, MMP-9 and MMP-13 have common regulatory elements in their promoter regions responding to inflammatory stimuli (33) and compose a posttranscriptional proteolytic cascade (34,35), these MMPs might promote the initial phase of tissue remodeling.…”

CD4+25+ Regulatory T Cells Limit Th1-Autoimmunity by Inducing IL-10 Producing T Cells Following Human Lung Transplantation

“…Matrix metalloproteinases (MMPs)-2,9 are capable of cleaving collagen molecules (41). Further, the activity of MMP-2 and MMP-9 has been shown to get upregulated after LT mainly during allograft rejection (42,43). In fact, col-V has been detected in the bronchoalveolar lavage fluid in human and rat lung allografts (13,44).…”