Endothelial cell surface alkaline phosphatase activity is induced by IL-6 released during wound repair.
Phosphatase activity on endothelial cell surfaces is responsible, in part, for the conversion of adenosine nucleotides to adenosine, a potent 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 following injury, the effect of tissue fluids collected from porcine or human skin wounds was tested on primary cultures of endothelial cells. Phosphatase activity increased approximately 50-fold following 48-h culture in the presence of wound fluid. Inductive activity was present only in fluids collected during the inflammatory phase of wound repair. The phosphatase activity metabolized adenosine monophosphate to free phosphate and was the liver/bone/kidney alkaline phosphatase isoenzyme: activity was temperature- and levamisole-sensitive, 1-phenylalanine-resistant, 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 cytokines, leukaemia inhibiting factor, and oncostatin M, caused a similar degree of alkaline phosphatase induction. Therefore, following injury, accumulation of interleukin-6 can lead to production by alkaline phosphatase of adenosine and subsequent protection from ischemic injury.
Gallo
R L
RL
Department of Dermatology, Joint Program of Neonatology, Children's Hospital, Boston, Massachusetts 02115, U.S.A.
Dorschner
R A
RA
Takashima
S
S
Klagsbrun
M
M
Eriksson
E
E
Bernfield
M
M
D000249:Adenosine Monophosphate / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism; D001826:Body Fluids / Q000502:physiology; D001842:Bone and Bones / Q000201:enzymology; D002417:Cattle; D002462:Cell Membrane / Q000201:enzymology; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology*; D004790:Enzyme Induction; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D010766:Phosphorylation; D013552:Swine; D014945:Wound Healing / Q000502:physiology*; D014947:Wounds and Injuries / Q000378:metabolism
D015850:Interleukin-6; D007527:Isoenzymes; D000249:Adenosine Monophosphate; D000469:Alkaline Phosphatase