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.

Abstract

The effect of soluble factors from the monocyte/macrophage (M0) 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 M0s were isolated by adherence or in a Percoll gradient, and alveolar M0s were obtained by lavage. Conditioned medium (CM) was prepared by preincubating M0s with medium alone or by separating SMC and M0 cocultures by a membrane insert Cell proliferation (image analysis) and 6-ketoprostaglandin F 1<r (6-keto-PGF la , radioimmunoassay) were measured in SMCs. Labeled prostanoids and other eicosanoid metabolites were isolated by high-performance liquid chromatography from SMCs prelabeled with 14 C-AA. M0s did not synthesize 6-keto-PGF Io . The CM enhanced proliferation but did not stimulate 6-keto-PGFi«, synthesis in SMCs. However, cell-cell contact in cocultures of SMCs with the same concentration of M0s used to generate CM resulted in increased 6-keto-PGF la 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 M0s. 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 A A 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. LJpoxygenase and other products of AA were not formed through cell-cell contact. These data showed that M0s express a soluble factor that enhances SMC proliferation without affecting prostanoid synthesis. Subsequent cell contact between SMCs and M0s stimulates prostanoid synthesis, which may possibly serve as a local and focal homeostatic mechanism for the regulation of uncontrolled SMC proliferation in atherogenesis.

Role of interleukin-1 receptor 1/MyD88 signalling in the development and progression of pulmonary hypertension

“…To further delineate the role for IL-1β in mediating the effects of macrophages on PA-SMC proliferation, we examined the effects of media conditioned by macrophages from WT and M.lys-Cre MyD88 fl/fl mice, with culture conditions that produced M0, M1 and M2 macrophages. As previously reported [33,34], we found that conditioned medium from any of these three macrophage types stimulated PA-SMC growth, with greater effects of M2 compared to M1 macrophages, and of M1 compared to M0 macrophages. An effect on PA-SMC growth of macrophage-derived IL-1β was clearly shown with M1 macrophages, since the stimulatory effect of the macrophage medium was reduced by anakinra.…”

Monocyte/Macrophage Regulation of Vascular Calcification In Vitro

“…A similar cell-cell contact requirement has been reported for M/M stimulation of prostanoid synthesis in vascular smooth muscle cells. 33 Cell-cell interaction between monocytes and CVCs could be operating through engagement of cell-surface integrins with extracellular matrix proteins. Integrins such as ␣-2 regulate osteoblastic differentiation and mineralization in vitro through binding to the extracellular matrix protein osteopontin.…”

On Radiation Damage to Normal Tissues and its Treatment: II. Anti-inflammatory drugs

“…Singling out the direct endothelial damage by radiation as a primary event is not supported either by the common knowledge that, whereas the microvasculature may be affected, the major blood vessels are mostly spared. Within the narrower scope of this part of the review which focuses on bioactive arachidonic acid dcrivatives, the possibility of blood vessel changes after irradiation being regulatory in character and caused at least in part indirectly (i.e., mediated by diffusible species also generated in nonvascular cells) is further supported by studies on heterologous cell-cell interactions in eicosanoid synthesis (66)(67)(68)(69)(70)(71)(72)(73)(74)(75)(76)(77)(78)(79). There seems therefore to be insufficient reason for investigating only the endothelium and vascular smooth muscle cells in an attempt to unravel radiationinduced changes in blood vessels; responses of the intervening (i.e., other stromal and parenchymal) and bloodcirculating cells, as well as reciprocal cell interactions must be taken into account.…”