Interactions between the monocyte/macrophage and the vascular smooth muscle cell: Stimulation of mitogenesis by a soluble factor and of prostanoid synthesis by cell-cell contact

Hanfang Zhang, Elizabeth C. Downs, Jenifer A. Lindsey, W. Bruce Davis, Ronald L. Whisler, David G. Cornwall

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

The effect of soluble factors from the monocyte/macrophage (MØ) on cell proliferation and the functional effects of cell-cell contact on the arachidonic acid (AA) cascade were studied with vascular smooth muscle cells (SMCs). Peripheral blood MØs were isolated by adherence or in a Percoll gradient, and alveolar MØs were obtained by lavage. Conditioned medium (CM) was prepared by preincubating MØs with medium alone or by separating SMC and MØ cocultures by a membrane insert. Cell proliferation (image analysis) and 6-ketoprostagIandin F (6-keto-PGF, radioimmunoassay) were measured in SMCs. Labeled prostanoids and other eicosanoid metabolites were isolated by high-performance liquid chromatography from SMCs prelabeled with 14C-AA. MØs did not synthesize 6-keto-PGF. The CM enhanced proliferation but did not stimulate 6-keto-PGF synthesis in SMCs. However, cell-cell contact in cocultures of SMCs with the same concentration of MØs used to generate CM resulted in increased 6-keto-PGF synthesis by SMCs. Since the stimulatory effect of cell contact was not blocked by butylated hydroxytoluene, it could not be attributed to an oxidative burst from MØs. Functional studies showed that the stimulatory effect of cell contact was enhanced by exogenous free AA and by endogenous AA release through A23187. Release of total radioactivity from prelabeled SMCs was enhanced by cell contact, and this effect was blocked by indomethacin (IM). Cell contact did not increase the release of free AA from prelabeled SMCs, even in the presence of IM. Finally, cell contact only stimulated the formation of prostanoids (IM-sensitive eicosanoid metabolites) from prelabeled SMCs. Lipoxygenase and other products of AA were not formed through cell-cell contact. These data showed that MØs express a soluble factor that enhances SMC proliferation without affecting prostanoid synthesis. Subsequent cell contact between SMCs and MØs stimulates prostanoid synthesis, which may possibly serve as a local and focal homeostatic mechanism for the regulation of uncontrolled SMC proliferation in atherogenesis.

Original languageEnglish (US)
Pages (from-to)220-230
Number of pages11
JournalArteriosclerosis, thrombosis, and vascular biology
Volume13
Issue number2
DOIs
StatePublished - Jan 1 1993

Keywords

  • Arachidonic acid cascade
  • Cell-cell contacts
  • Monocytes
  • Proliferation
  • Prostanoids
  • Smooth muscle cells

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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