It is known that human neutrophils (PMNs) stimulated by mechanical agitation cause an increase in the pulmonary vascular permeability. However, it is not clear whether these stimulated PMNs give signals to endothelial cells and these signals cause the permeability change. We hypothesized that the protein kinase C within the endothelial cells, one of the important enzyme for the intracellular signal transduction, involved with this permeability change. The pulmonary vascular injury was assessed by measuring pulmonary vascular filtration coefficient (K) using a gravimetric method. Stimulation of human PMNs was obtained by agitating them in a glass container for 10 seconds. After measuring the K under the baseline condition, either GF109023X (50 uM), a protein kinase C inhibitor, or saline was added in perfusate, and incubated for 30 minutes. Then the perfusate was changed to that of GF109023X free to avoid the effect onto PMNs. We gave either stimulated or stimulation free PMNs into the perfusate (at the final concentration of 25 cells/ul) and measured the K after 90 minutes incubation. Stimulated PMNs induced a 5 fold increase in the K value compared to unstimulated PMNs group. This increase in the K by stimulated PMNs was partially blocked by the pretreatment of GF109023X. These results suggest that the mechanically stimulated PMNs adhered to the endothelial cells injure the pulmonary vascular endothelial cells through protein kinase C.
|Publication status||Published - 1998 Mar 20|