Abstract
Recent investigations have emphasized the role of activated granulocytes in mediating vascular endothelial injury in the pathogenesis of shock lung. In vitro studies have indicated that tight adherence of the neutrophil to the endothelium is crucial for the development of cellular injury. Fibronectin is critical to cell-to- substratum and cell-to-cell interactions. Since fibronectin resides in plasma, on endothelial cell surfaces and is secreted into cell matrices, the adhesive properties of fibronectin must be modulated, lest universal cell agglomeration occur, yet be enhanced when cell attachment is appropriate. In these studies, treatment of fibronectin- coated surfaces with neutrophil release products increased the adhesion of activated neutrophils. Similarly, endothelial cells treated with neutrophil release products become a more adherent substrate for neutrophils. This enhanced adherence generated by treatment of fibronectin with neutrophil supernatants is inhibitable by heat and the lysosomal proteinase inhibitor, pepstatin-A. Neutrophil release products cause proteolytic fragmentation of fibronectin and enhanced fibronectin immunofluorescence on endothelial cells. In addition, neutrophils are more injurious to endothelial cells that have been pretreated with neutrophil release products. Neutrophils may enhance their own adherence to endothelial cells by altering fibronectin, and this altered, or “inflamed,” fibronectin may serve as an amplifier of inflammation.
