Tumor-promoting phorbol esters inhibit monocyte adherence to endothelial cells

Monocyte adherence to endothelial cells (EC) is an important event in the development of a monocytic inflammatory response, yet the effects of inflammatory mediators on monocyte adherence to EC are not well described. We compared the effects of phorbol esters known to activate protein kinase C, including phorbol myristate acetate (PMA) and phorbol 12,13-dibutyrate (PDA), on monocyte adherence to bovine aortic EC. Human monocytes (purity 90 +/- 1% SE) were isolated by centrifugal elutriation to obtain monocytes not previously exposed to a surface. Kinetic studies revealed that 51Cr-labeled monocyte adherence to EC reached a plateau after a 45-min incubation. Concentrations of PMA between 10 and 1,000 ng/ml significantly decreased monocyte adherence to EC (26 +/- 10 and 35 +/- 8% decrease compared with control, respectively). Concentrations of PDA of 100 and 1,000 ng/ml had a similar inhibitory effect. In contrast, the chemotactic stimulus, zymosan-activated serum, significantly increased monocyte adherence (40 +/- 14% increase compared with control). Thus inflammatory stimuli have different effects on the adhesive interaction of monocytes to EC. This may provide a mechanism to selectively modulate monocyte egress from the circulation into extravascular inflammatory sites.