Human monocyte colony-stimulating factor stimulates the gene expression of monocyte chemotactic protein-1 and increases the adhesion of monocytes to endothelial monolayers

Yeun Jund Shyy, Lori L. Wickham, Joseph P. Hagan, Hsyue Jen Hsieh, Ying Li Hu, Simon H. Telian, Anthony J. Valente, K. L. Paul Sung, Shu Chien

Research output: Contribution to journalArticle

80 Scopus citations

Abstract

The stimulation of the human umbilical vein endothelial cell (HUVEC) with recombinant human monocyte-derived colony-stimulating factor (MCSF) increased the gene expression of monocyte chemotactic protein (MCP-1). Northern blot analysis indicated that 50 U/ml of MCSF is the optimal concentration for this effect. The elevation of MCP-1 mRNA started as early as 1 h after stimulation and was maintained for at least 8 h. An increased MCP-1 level in MCSF-treated HUVEC was also demonstrated at the protein level by immunocytochemical staining using a polyclonal MCP-1-specific antibody. HUVEC activated by 50 U/ml of MCSF for 5 h showed a stronger immunofluorescence staining than control cells. Micropipette separation of THP-1 monocytes from HUVEC showed that the activation of both THP-1 and endothelium by MCSF led to an increase in the separation force by more than three times (36.2±6.7 × 10-4vs.9.6±3.6 × 10-4dyn). An increased adhesiveness was also observed after MCSF activation of peripheral blood monocytes and HUVEC (16.7±2.7 × 10-4 vs. 5.2±0.9 × 10-4 dyn). The increased adhesive force in both systems was blocked by the use of anti-MCP-1 (5.5±0.8 × 10-4 and 6.8±1.1 × 10-4 dyn). Similar results were obtained in experiments in which only HUVEC, but not monocytes, were activated by MCSF. This increased adhesion of untreated monocytes to MCSF-activated HUVEC was also blocked by the addition of anti-MCP-1. In contrast, experiments in which only THP-1 or peripheral blood monocytes, but not HUVEC, were treated with MCSF did not show a significant increase of adhesion between these cells. These results indicate that MCSF augments monocyte-endothelium interaction primarily by its action on the endothelial cell and that this function is probably mediated through an increased expression of MCP-1. The MCSF/MCP-1-dependent adhesive mechanism might be operative in the arterial wall in vivo to lead to the trapping of the infiltrated monocyte-macrophage in the subendothelial space during atherogenesis.

Original languageEnglish (US)
Pages (from-to)1745-1751
Number of pages7
JournalJournal of Clinical Investigation
Volume92
Issue number4
DOIs
StatePublished - 1993

Keywords

  • Atherosclerosis
  • Cellular interaction
  • Chemotaxis
  • Micropipette aspiration
  • Monocyte infiltration

ASJC Scopus subject areas

  • Medicine(all)

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