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GM‐CSF activates RhoA, integrin and MMP expression in human monocytic cells
Author(s) -
Kohno Yukari,
Tanimoto Akihide,
Cirathaworn Cintana,
Shimajiri Shohei,
Tawara Akihiko,
Sasaguri Yasuyuki
Publication year - 2004
Publication title -
pathology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.73
H-Index - 74
eISSN - 1440-1827
pISSN - 1320-5463
DOI - 10.1111/j.1440-1827.2004.01682.x
Subject(s) - rhoa , integrin , monocyte , microbiology and biotechnology , matrix metalloproteinase , extracellular matrix , chemistry , cancer research , biology , immunology , signal transduction , cell , biochemistry
Monocyte migration is one of the key events occurring in the early stage of atherosclerosis. This process includes monocytic adhesion to and penetration through the arterial intima. In such an environment, many factors stimulate the monocytes to enhance integrin activation and extracellular matrix degradation. To investigate the coordinative operation of these two events in relation to monocyte migration, we paid particular attention to the effects of granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) on monocytes in terms of RhoA activation and matrix metalloproteinase (MMP) expression. RhoA and integrin clustering were activated by GM‐CSF, monocyte chemoattractant protein‐1 (MCP‐1) and platelet‐derived growth factor‐BB (PDGF‐BB) in human monocytic cell lines. Furthermore, enhancement of migration was observed with stimulation by MCP‐1 and PDGF‐BB. Granulocyte‐macrophage colony‐stimulating factor did not enhance the migration, even though it activated RhoA and integrin. However, GM‐CSF is known to stimulate monocytes to express MCP‐1, suggesting the presence of an indirect mechanism for GM‐CSF‐mediated migratory activity. In contrast, only GM‐CSF enhanced the expression of MMP‐1 and MMP‐9. These results provide evidence that GM‐CSF has multiple functions enhancing monocytic migration via RhoA and integrin activation, and via MMP expression.