ENDOTHELIAL-CELL SURFACE ALKALINE-PHOSPHATASE ACTIVITY IS INDUCED BY IL-6 RELEASED DURING WOUND REPAIR

Phosphatase activity on endothelial cell surfaces is responsible, in p art, for the conversion of adenosine nucleotides to adenosine, a poten t vasodilator and anti-inflammatory mediator that can protect tissues from the ischemic damage that results from injury. To evaluate whether phosphatases are actively induced by a soluble factor released follow ing injury, the effect of tissue fluids collected from porcine or huma n skin wounds was tested on primary cultures of endothelial cells. Pho sphatase activity increased approximate to 50-fold following 48-h cult ure in the presence of wound fluid. Inductive activity was present onl y in fluids collected during the inflammatory phase of wound repair. T he phosphatase activity metabolized adenosine monophosphate to free ph osphate and was the liver/bone/kidney alkaline phosphatase isoenzyme: activity was temperature- and levamisole-sensitive, 1-phenylalanine-re sistant, and linked to the cell surface via phospholipid, and migrated at a size identical to this isozyme. interleukin-6 was identified as the phosphatase-inducing factor in wound fluid and the related cytokin es, leukaemia inhibiting factor and oncostatin M, caused a similar deg ree of alkaline phosphatase induction. Therefore, following injury, ac cumulation of interleukin-6 can lead to production by alkaline phospha tase of adenosine and subsequent protection from ischemic injury.