Pulmonary alveolar macrophages from patients with active sarcoidosis express type IV collagenolytic proteinase. An enzymatic mechanism for influx of mononuclear phagocytes at sites of disease activity.

Agostini, Carlo; Garbisa, Spiridione; Trentin, Livio; Zambello, Renato; Fastelli, G; Onisto, Maurizio; Cipriani, A; Festi, Giuliana; Casara, Dario; Semenzato, Gianpietro

doi:10.1172/jci114205

Cited by 30 publications

(18 citation statements)

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“…An elevated expression of monocyte-lineage surface antigens was found on AMs from patients with sarcoidosis [13,14,17,[35][36][37][38], idiopathic pulmonary fibrosis [15,16,[36][37][38], extrinsic allergic alveolitis [36,37], bronchogenic carcinoma [35], asthma [39], human immunodeficiency virus (HIV) infection [40], as well as in smoking individuals [41,42]. The increased expression of binding sites for several lectins by AMs from patients with interstitial lung disease may reflect the influx of immature blood monocytes and/or the emergence of a proinflammatory macrophage phenotype [43].…”

Section: Discussionmentioning

confidence: 99%

“…a monocyte-like immunophenotype of the total AM population, displaying increased expression of CD14 [13,14,17,35] and CD11b [35,38], and reduced expression of CD16. Our quantitative flow cytometric analyses, however, extend these findings in that they demonstrate that in the BAL fluid of patients with chronic inflammatory lung disease increased numbers of monocyte-like cells can be identified that exhibit the electrooptical characteristics of blood monocytes and an immunophenotype intermediate between blood monocytes and AMs.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, MCP-1 was found to be intensely expressed in lung tissue [11] and bronchoalveolar lavage (BAL) fluid of patients with interstitial lung disease [12]. Several studies described a monocyte-like phenotype of AMs in chronic inflammatory lung diseases, possibly reflecting the influx of blood monocytes and/or the emergence of a proinflammatory macrophage phenotype [13][14][15][16][17].…”

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confidence: 99%

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Characterization and quantification of alveolar monocyte-like cells in human chronic inflammatory lung disease

Krombach

Gerlach²,

Padovan³

et al. 1996

Eur Respir J

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Characterization and quantification of alveolar monocyte-like cells in human chronic inflammatory lung disease

Krombach

Gerlach²,

Padovan³

et al. 1996

Eur Respir J

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“…Gelatinases of 67-72 kDa and of 90 kDa have been isolated from bronchial lavage or alveolar macrophages [7,33]. Upregulation in alveolar macrophages of a 90-kDa gelatinase by Escherichia coli endotoxin, was recently described f33].…”

Section: Discussionmentioning

confidence: 99%

Natural human monocyte gelatinase and its inhibitor

et al. 1991

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Gelatinases produced by stimulated peripheral blood monocytes were detected by substrate zymography and were compared with those derived from tumor cells. Stimulated monocytes were found to produce an 85 kDa gelatinase which co-migrated upon electrophoretic separation and crossreacted in immunoprecipitat.ion experiments with a phorbol ester inducible metalloprotease from human tumor cells. The intact natural gelatinase (85 kDa), a high molecular weight and complexed gelatinase as well as a proteolytic fragment (25 kDa) were purified by substrate-and antibody affinity chromatography techniques. Aminoterminal sequence analysis showed that natural monocyte gelatinase occurs as a truncated form of tumor cell gelatinase/type IV collagenase. Furthermore, peripheral blood monocytes were found to also produce a tissue inhibitor of metalloproteases (TIMP). TIMP was co-purified with gelatinase on gelatin sepharose and identified by microsequencing. The balanced and regulated production of gelatinase and TIMP might be important in monocyte migration and tissue remodeling.

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“…These studies suggest that an imbalance in MMP-9 and TIMP-1 production may be linked to the development of submucosal fibrosis in these patients. Elevated production of MMP-9 by alveolar macrophages from both IPF and sarcoidosis patients has been reported [18,19]. Against this background, the aim of the present study was to evaluate 1) the contribution of the three collagenolytic MMPs to collagenase levels; and 2) the relative concentrations of MMP-9/TIMP-1 in BALF from patients with established fibrosis (IPF) and sarcoidosis with different degrees of pulmonary involvement.…”

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confidence: 95%

Matrix metalloproteinases and tissue inhibitor of metalloproteinase-1 in sarcoidosis and IPF

Henry¹,

McMahon²,

Mackarel³

et al. 2002

European Respiratory Journal

139

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The purpose of this study was to examine the role of interstitial collagenases, members of the family of matrix metalloproteinases, in the development of pulmonary fibrosis.The activity, levels and molecular forms of collagenases (matrix metalloproteinases (MMP)-1, -8 and -13), gelatinase B (MMP-9) and its main endogenous inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1) were assessed in bronchoalveolar lavage fluid (BALF) from patients with idiopathic pulmonary fibrosis (IPF) and sarcoidosis patients with varying degrees of pulmonary parenchymal involvement.Collagenase activity was elevated in IPF and group 3 sarcoidosis patients. A positive correlation between BALF collagenase activity and MMP-8 levels was also observed. Western immunoblotting revealed the presence of two isoforms of MMP-8 in patient samples; an 80 kD form representing latent enzyme from polymorphonuclear neutrophils and a 55 kD form representing the fibroblast-type proform. MMP-9 levels were also elevated in both IPF and group 3 sarcoidosis patients, while TIMP-1 levels remained normal, indicating a shift in the balance between the enzyme and inhibitor, favouring MMP-9.Matrix metalloproteinase-8 is the major contributor to the bronchoalveolar lavage fluid collagenase activity in the airways of patients with idiopathic pulmonary fibrosis and sarcoidosis and may initiate collagen destruction and remodelling leading to the development of pulmonary fibrosis.

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Pulmonary alveolar macrophages from patients with active sarcoidosis express type IV collagenolytic proteinase. An enzymatic mechanism for influx of mononuclear phagocytes at sites of disease activity.

Abstract: Alveolar macrophages (AMs) recovered from the bronchoal-

Cited by 30 publications

References 24 publications

Characterization and quantification of alveolar monocyte-like cells in human chronic inflammatory lung disease

Characterization and quantification of alveolar monocyte-like cells in human chronic inflammatory lung disease

Natural human monocyte gelatinase and its inhibitor

Matrix metalloproteinases and tissue inhibitor of metalloproteinase-1 in sarcoidosis and IPF

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