期刊
AMERICAN JOURNAL OF PATHOLOGY
卷 156, 期 5, 页码 1797-1804出版社
AMER SOC INVESTIGATIVE PATHOLOGY, INC
DOI: 10.1016/S0002-9440(10)65051-1
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- NHLBI NIH HHS [HL-61794, HL-54759] Funding Source: Medline
When the monocyte infiltrates a tissue, adhesion to the extracellular matrix provides structural anchors, and the cell may be deformed through these attachments. To test the hypothesis that human monocytes/macrophages are mechanically responsive, we studied the effects of small cyclic mechanical deformations on cultured human monocytes/macrophages. When monocytes/macrophages were subjected to 4% strain at 1 Hz for 24 hours, neither matrix metalloproteinase (MMP)-1 nor MMP-3 was induced; however, in the presence of phorbol myristate acetate, strain augmented MMP-1 expression by 5.1 +/- 0.7-fold(P < 0.05) and MMP-3 expression by 1.6 +/- 0.1-fold (P < 0.05). In contrast, MMP-9 expression was not changed by mechanical strain in the presence or absence of phorbol myristate acetate. Deformation rapidly induced the immediate early response genes c-fos and c-jun. In addition, mechanical deformation induced the transcription factor PU.1, an ets family member that is essential in monocyte differentiation, as well as mRNA for the M-CSF receptor. These studies demonstrate that human monocytes/macrophages respond to mechanical deformation with selective augmentation of MMPs, induction of immediate early genes, and induction of the M-CSF receptor. In addition to enhancing the proteolytic activity of macrophages within repairing tissues, cellular deformation within tissues may play a role in monocyte differentiation.
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