BACKGROUND: Matrix metalloproteinases (MMPs) have been shown to be involved in the pathogenesis of the destructive pulmonary lesions in patients with lymphangioleiomyomatosis (LAM); in the present report, the activation of these enzymes is examined. OBJECTIVE: To evaluate the role of MMPs and their activating enzymes, immunohistochemical and confocalmicroscopic techniques were used to localize alpha-smooth muscle actin (alpha-SMA), HMB-45, proliferating cell nuclear antigen (PCNA), MMP-2, membrane-type 1 MMP (MT1-MMP), MT2-MMP, and MT3-MMP in lung tissues from 10 women with LAM. Tissue samples were obtained from 5 patients before treatment and in 5 patients after hormone treatment (progesterone and/or tamoxifen citrate). RESULTS: Staining for alpha-SMA and MMP-2 was present in all the abnormal smooth muscle cells (LAM cells) in both groups. The percentages of PCNA-, MMP-2-, or MT1-MMP-positive LAM cells were much higher in the untreated group than in the treated group, whereas the percentages of HMB-45-reactive LAM cells were similar in both groups. The reactions for MT1-MMP and PCNA were preferentially localized in small spindle-shaped LAM cells; the reaction for HMB-45 was found in large epithelioid LAM cells. Many of the PCNA-positive cells were also positive for MT1-MMP. Staining for MT2-MMP and MT3-MMP was negative. CONCLUSIONS: This study demonstrates an association between cellular proliferation and the presence of MT1-MMP in LAM cells. The activation of MMP-2 by MT1-MMP may play an important role in the destruction of lung tissue in this disorder.
BACKGROUND: Matrix metalloproteinases (MMPs) have been shown to be involved in the pathogenesis of the destructive pulmonary lesions in patients with lymphangioleiomyomatosis (LAM); in the present report, the activation of these enzymes is examined. OBJECTIVE: To evaluate the role of MMPs and their activating enzymes, immunohistochemical and confocalmicroscopic techniques were used to localize alpha-smooth muscle actin (alpha-SMA), HMB-45, proliferating cell nuclear antigen (PCNA), MMP-2, membrane-type 1 MMP (MT1-MMP), MT2-MMP, and MT3-MMP in lung tissues from 10 women with LAM. Tissue samples were obtained from 5 patients before treatment and in 5 patients after hormone treatment (progesterone and/or tamoxifen citrate). RESULTS: Staining for alpha-SMA and MMP-2 was present in all the abnormal smooth muscle cells (LAM cells) in both groups. The percentages of PCNA-, MMP-2-, or MT1-MMP-positive LAM cells were much higher in the untreated group than in the treated group, whereas the percentages of HMB-45-reactive LAM cells were similar in both groups. The reactions for MT1-MMP and PCNA were preferentially localized in small spindle-shaped LAM cells; the reaction for HMB-45 was found in large epithelioid LAM cells. Many of the PCNA-positive cells were also positive for MT1-MMP. Staining for MT2-MMP and MT3-MMP was negative. CONCLUSIONS: This study demonstrates an association between cellular proliferation and the presence of MT1-MMP in LAM cells. The activation of MMP-2 by MT1-MMP may play an important role in the destruction of lung tissue in this disorder.
Authors: Elena A Goncharova; Dmitriy A Goncharov; Poay N Lim; Daniel Noonan; Vera P Krymskaya Journal: Am J Respir Cell Mol Biol Date: 2005-12-30 Impact factor: 6.914
Authors: Nishant Gupta; Robert Vassallo; Kathryn A Wikenheiser-Brokamp; Francis X McCormack Journal: Am J Respir Crit Care Med Date: 2015-07-01 Impact factor: 21.405
Authors: Andrew R Osterburg; Rebecca L Nelson; Benyamin Z Yaniv; Rachel Foot; Walter Rf Donica; Madison A Nashu; Huan Liu; Kathryn A Wikenheiser-Brokamp; Joel Moss; Nishant Gupta; Francis X McCormack; Michael T Borchers Journal: JCI Insight Date: 2016-10-06
Authors: Francis X McCormack; Nishant Gupta; Geraldine R Finlay; Lisa R Young; Angelo M Taveira-DaSilva; Connie G Glasgow; Wendy K Steagall; Simon R Johnson; Steven A Sahn; Jay H Ryu; Charlie Strange; Kuniaki Seyama; Eugene J Sullivan; Robert M Kotloff; Gregory P Downey; Jeffrey T Chapman; MeiLan K Han; Jeanine M D'Armiento; Yoshikazu Inoue; Elizabeth P Henske; John J Bissler; Thomas V Colby; Brent W Kinder; Kathryn A Wikenheiser-Brokamp; Kevin K Brown; Jean F Cordier; Cristopher Meyer; Vincent Cottin; Jan L Brozek; Karen Smith; Kevin C Wilson; Joel Moss Journal: Am J Respir Crit Care Med Date: 2016-09-15 Impact factor: 21.405
Authors: Chenggang Li; Xiaobo Zhou; Yang Sun; Erik Zhang; John D Mancini; Andrey Parkhitko; Tasha A Morrison; Edwin K Silverman; Elizabeth P Henske; Jane J Yu Journal: Am J Respir Cell Mol Biol Date: 2013-07 Impact factor: 6.914