Collagen type I alters the proteomic signature of macrophages in a collagen morphology-dependent manner

Abstract

Idiopathic pulmonary fibrosis is a progressive lung disease that causes scarring and loss of lung function. Macrophages play a key role in fibrosis, but their responses to altered morphological and mechanical properties of the extracellular matrix in fibrosis is relatively unexplored. Our previous work showed functional changes in murine fetal liver-derived alveolar macrophages on fibrous or globular collagen morphologies. In this study, we applied differential proteomics to further investigate molecular mechanisms underlying the observed functional changes. Macrophages cultured on uncoated, fibrous, or globular collagen-coated plastic were analyzed by liquid chromatography-mass spectrometry. The presence of collagen affected expression of 77 proteins, while 142 were differentially expressed between macrophages grown on fibrous or globular collagen. Biological process and pathway enrichment analysis revealed that culturing on any type of collagen induced higher expression of enzymes involved in glycolysis. However, this did not lead to a higher rate of glycolysis, probably because of a concomitant decrease in activity of these enzymes. Our data suggest that macrophages sense collagen morphologies and can respond with changes in expression and activity of metabolism-related proteins. These findings suggest intimate interactions between macrophages and their surroundings that may be important in repair or fibrosis of lung tissue.

The interplay of collagen, macrophages, and microcalcification in atherosclerotic plaque cap rupture mechanics

“…Finally, the collagenous matrix itself plays an important role in regulating various processes of macrophage biology, including monocyte-to-macrophage differentiation, lipid uptake [ 258 ], metabolism [ 244 ], polarization [ 131 ], migration mode [ 86 ] as well as their ability to secrete proteases [ 138 , 258 ]. It has been shown in vitro that macrophages increase their MMP-9 secretion when cultured on monomeric type I collagen, in comparison to when they were exposed to the polymerized variant [ 138 ].…”

Modulation of macrophages by biophysical cues in health and beyond

“…Collagens makes up a large part of the ECM, along with fibronectin, elastin, laminin, tenascin, nidogen, and glycosaminoglycans and their proteoglycans. Macrophages sense collagen morphologies and respond with changes in the expression and activity of metabolism-related proteins [ 12 ]. It is well documented that macrophages cultured in vitro on distinct matrix substrates, elicit different responses, for example, rate of growth, morphology, and expression of inflammatory mediators, which are different from those cultured directly on tissue culture plastics [ 12 , 54 ].…”

“…Macrophages sense collagen morphologies and respond with changes in the expression and activity of metabolism-related proteins [ 12 ]. It is well documented that macrophages cultured in vitro on distinct matrix substrates, elicit different responses, for example, rate of growth, morphology, and expression of inflammatory mediators, which are different from those cultured directly on tissue culture plastics [ 12 , 54 ]. Luu TU and co-authors demonstrated a more anti-inflammatory phenotype when macrophages were cultured on laminin and vitronectin, ECM components that proportionally increase in tumours where macrophages contribute to pathology [ 55 ].…”