The functional response of U937 macrophage-like cells is modulated by extracellular matrix proteins and mechanical...

Extracellular matrix proteins (ECMs) play a significant role in the transfer of mechanical strain to monocyte-derived macrophages (MDMs) affecting morphological changes in a foreign body reaction. This study investigated how the functional responses of U937 macrophage-like cells differed when subjected to 2 dynamic strain types (nonuniform biaxial or uniform uniaxial strain) while cultured on siloxane membranes coated with either collagen type I or RGD peptide repeats (ProNectin). Biaxial strain caused an increase in intracellular esterase and acid phosphatase (AP) activities, as well as monocyte-specific esterase (MSE) protein levels in cells that were seeded on either uncoated surfaces (shown previously) or collagen, but not ProNectin. Released AP activity, but not released esterase activity, was increased on all surfaces. Biaxial strain increased IL-6, but not IL-8 on all surfaces. When cells were subjected to uniaxial strain, intracellular esterase increased on coated surfaces only, whereas intracellular AP activity was unaffected. Both esterase and AP released activities increased on all surfaces. Uniaxial strain increased the release of IL-6 on all surfaces, but IL-8 on coated surfaces only. This study demonstrated for the first time that ECM proteins could specifically modulate cellular responses to different types of strain. Using this approach with an in vitro cell system may help to unravel the complex function of MDMs in the foreign-body reaction.