Induction of Macrophage Matrix Metalloproteinase Biosynthesis by Surfactant Protein D

Abstract

Recent studies strongly suggest that surfactant protein D (SP-D) plays important roles in pulmonary host defense and the regulation of immune and inflammatory reactions in the lung. Although SP-D can bind to alveolar macrophages and can elicit their chemotaxis, relatively little is known about the direct cellular consequences of SP-D on the function of these cells. Because matrix metalloproteinases (MMPs) are synthesized in increased amounts in response to various proinflammatory stimuli, we investigated the capacity of SP-D to modulate the production of MMPs by freshly isolated human alveolar macrophages. Unexpectedly we found that recombinant rat SP-D dodecamers selectively induce the biosynthesis of collagenase-1 (MMP-1), stromelysin (MMP-3), and macrophage elastase (MMP-12) without significantly increasing the production of tumor necrosis factor ␣ and interleukin-1␤. SP-D did not alter the production of these MMPs by fibroblasts. Phosphatidylinositol, a surfactant-associated ligand that interacts with the carboxyl-terminal neck and carbohydrate recognition domains of SP-D, inhibited the SP-D-dependent increase in MMP biosynthesis. A trimeric, recombinant protein consisting of only the neck and carbohydrate recognition domain did not augment metalloproteinase production, suggesting that the stimulatory effect on MMP production depends on an appropriate spatial presentation of trimeric lectin domains. Although SP-D dodecamers can selectively augment metalloproteinase activity in vitro, this effect may be competitively inhibited by tissue inhibitors of metalloproteinases or surfactant-associated ligands in vivo.Surfactant protein D (SP-D) 1 is a member of the collectin subfamily of C-type lectins that also includes surfactant protein A and the serum protein mannose-binding protein (1-3). In

A study of inflammatory biomarkers in crystalline silica exposed rock drillers

“…We also observed significantly higher SP-D concentrations in these exposed rock drillers as previously reported (Ellingsen et al 2022 ), SP-D has been shown to induce MMP-12 in human macrophages (Trask et al 2001 ). Associations between SP-D and MMP-12 have hardly been studied and should be addressed in future studies.…”

Surfactant proteins A and D in pregnancy and parturition

“…Antioxidants N-acetylcysteine and pyrrolidine dithiocarbamate inhibited MMP production by AMs from SP-D(-/-) mice (44). Trask et al, 2001, reported that recombinant rat SP-D dodecamers selectively induce the biosynthesis of collagenase-1 (MMP-1), stromelysin (MMP-3), and macrophage elastase (MMP-12) without significantly increasing the production of tumor necrosis factor alpha and interleukin-1beta (45). SP-D did not alter the production of these MMPs by fibroblasts.…”

A Tale of Two Proteolytic Machines: Matrix Metalloproteinases and the Ubiquitin–Proteasome System in Pulmonary Fibrosis

“…This seems counterintuitive, as an antifibrotic mediator is upregulated lung parenchyma, yet the lungs in IPF, by definition, become fibrotic. This can be explained by the preferential expression of MMP1 in different lung tissue: MMP1 overexpression is localized to the alveolar epithelial cells (AEC) and lung macrophages, allowing fibrosis elsewhere in the interstitial lung compartment [29][30][31][32]. Furthermore, MMP3 is believed to be involved in the pathogenesis of IPF by inducing epithelial to mesenchymal transition.…”