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Induction of Adhesion-dependent Signals Using Low-intensity Ultrasound
Published on: May 8, 2012
[Molecular mechanisms of low intensity pulsed ultrasound-mediated cellular behavior in human primary macrophages]
Yi-Ping Li1, Shao-Xia Zhou, Andreas Schmelz
1Department of Pathology, Basic Medical College of Southeast University, Nanjing 210009, China. lypzzm@yahoo.com.cn
Abstract:
The aim of this study was to explore the molecular mechanisms of the effect of low intensity pulsed ultrasound (LIPUS) on human primary macrophage functions. Macrophage phagocytosis was analyzed using fluorescein isothiocyanate (FITC)-labelled Escherichia coli (E.Coli); focal complex and extracellular matrix metalloproteinase inducer (EMMPRIN) were observed by fluorescence microscopy; the secretion of metalloproteinases (MMPs) was examined by gelatin zymography, and the expressions of EMMPRIN and extracellular signal-regulated kinases (ERKs) were detected by Western blot. The results indicated that LIPUS accelerated macrophages to phagocytose E.Coli (29.81+/-0.36 vs 18.00+/-0.78), promoted the protein expressions of EMMPRIN and MMPs, increased the level of protein tyrosine phosphorylation, and induced the phosphorylation of ERKs. Furthermore, the above functions were only found in adherent macrophages, and were inhibited or decreased by mitogen activated protein kinase kinase (MAPK kinase, MEK) inhibitor PD98059 and RGD (Arg-Gly-Asp peptide), one of main integrin recognition sequences. It is concluded that the effect of LIPUS on macrophages depends on cell adhesion, and relates to integrin-MEK-ERK pathway.
Insights
Low intensity pulsed ultrasound (LIPUS) enhances macrophage phagocytosis and promotes EMMPRIN and MMPs expression. This effect relies on cell adhesion and the integrin-MEK-ERK pathway.
Area of Science:
- Biomedical Engineering
- Cell Biology
- Immunology
Background:
- Low intensity pulsed ultrasound (LIPUS) is a non-invasive therapeutic modality.
- Macrophages play crucial roles in immune responses and tissue repair.
- Understanding LIPUS's molecular effects on macrophages is essential for therapeutic applications.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying LIPUS effects on human primary macrophage functions.
- To investigate the role of cell adhesion and specific signaling pathways in LIPUS-mediated macrophage activation.
Main Methods:
- Macrophage phagocytosis was assessed using FITC-labeled E. coli.
- Expression of EMMPRIN and focal complexes was visualized via fluorescence microscopy.
- Metalloproteinase (MMP) secretion was analyzed by gelatin zymography.
- Western blotting was employed to detect EMMPRIN and ERK phosphorylation.
Main Results:
- LIPUS significantly increased E. coli phagocytosis by macrophages (29.81±0.36 vs 18.00±0.78).
- LIPUS promoted EMMPRIN and MMP expression, increased tyrosine phosphorylation, and induced ERK phosphorylation.
- These effects were observed only in adherent macrophages and were inhibited by MEK inhibitor PD98059 and RGD peptide.
Conclusions:
- LIPUS-induced macrophage activation is dependent on cell adhesion.
- The integrin-MEK-ERK signaling pathway mediates the effects of LIPUS on macrophages.
