Studies on the mechanism of decreased neutrophil adherence to postconfluent cultured endothelial cells.

The adherence of neutrophils (PMN) to endothelium is a crucial early step in neutrophil-mediated vascular injury. However, vascular injury is not a necessary event in inflammatory states, which suggests that endogenous mechanisms may protect endothelial cells from neutrophil-mediated injury. Previous studies suggested that leukocytes adhered in greater numbers to vascular endothelium in vivo and in vitro, where the contiguity of the cells was disrupted and where endothelial cells were actively migrating and proliferating. We studied the effect of development of a confluent monolayer on adherence of human PMN to cultured bovine calf aortic endothelial cells and investigated several mechanisms by which this effect might occur. We found that adherence of quiescent and activated PMN decreased with development of a confluent endothelial cell monolayer. A similar effect was found using human umbilical-vein endothelial cells. In contrast, adherence of nylon wool-nonadherent, thymus-derived lymphocytes increased. Variation in neutrophil adherence was not due to adherence of PMN to exposed tissue culture plastic or to exposed matrix components in preconfluent cultures, nor due to products released into culture supernatants. Diminished PMN adherence to postconfluent monolayers may have been related to changes in endothelial cell glycoproteins because neuraminidase or cycloheximide pretreatment augmented PMN adherence to postconfluent cultures more than to preconfluent cultures. However, the extent of total cell surface sialation, as assessed by neuraminidase-releasable [3H]glucosamine from metabolically labeled monolayers, did not differ between pre- and postconfluent cultures, suggesting that some specific sialated cell surface constituent is responsible for decreased PMN adherence to postconfluent monolayers.(ABSTRACT TRUNCATED AT 250 WORDS)