Inhibition of human arterial smooth muscle cell growth by human monocyte/macrophages: a co-culture study

Monocyte/macrophages produce a variety of substances which may influence th e function of smooth muscle cells (SMC). During atherogenesis, macrophages are thought to modulate SMC migration, proliferation and synthesis of extra cellular matrix. Such modulation is the balance between stimulatory and inh ibitory influences. Thus, for example, our earlier studies have shown that macrophages not only secrete mitogens, but also produce small molecular wei ght inhibitors of SMC proliferation. In the present study, we have used a c o-culture system in which human monocyte/macrophages were separated from hu man arterial SMC (hSMC) by a filter with the optional addition of a 12 ka c ut-off dialysis membrane, in order to assess their effect on hSMC growth. W e have found that human peripheral blood-derived monocytes produced a subst ance of < 12 kDa that inhibited hSMC growth in the co-culture system. The m onocyte-derived factor causing this effect was completely blocked by indome thacin, indicating that growth-inhibitory factors produced by the monocytes were cyclooxygenase products. We have shown that PGE, and PGE, inhibit hSM C growth, making them likely candidates for the effector molecules released from monocytes in our co-culture system. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.