Local skin burn causes systemic (lung and kidney) endothelial cell injury reflected by increased circulating and decreased tissue factor VIII-related antigen.
Inasmuch as xanthine oxidase (XO)-derived O2* metabolites may contribute to vascular endothelial injury and Factor VIII antigen (F8Ag) is a component of endothelial cells, we hypothesized that XO-derived O2* might damage and cause distant organ endothelial cells to release F8Ag in rats subjected to skin burn. We found that serum F8Ag (ELISA) increased in the blood of rats subjected to skin burn (70 degrees C water to shaved dorsal skin for 30 seconds) but not in sham control rats (30 degrees C water). Coincidentally, F8Ag levels also decreased in lung and kidney tissue sections (immunofluorescent staining) of burned rats but not sham rats. Increases in circulating F8Ag levels and decreases in tissue F8Ag levels appeared to result from XO-derived O2* metabolites: F8Ag levels did not increase in the blood and did not decrease in the tissues of rats pretreated with allopurinol (a specific XO inhibitor, 50 mg/kg) or dimethylthiourea (DMTU) (a permeable O2* metabolite scavenger, 250 mg/kg). Lung injury as assessed by permeability studies (I125-albumin leak) paralleled changes in blood F8Ag levels in sham, burn, allopurinol-, and DMTU-treated groups. We conclude that skin burn causes a systemic vascular injury that can be inhibited by allopurinol or DMTU and is reflected by increased circulating and tissue decreased Factor VIII antigen levels. Release of Factor VIII antigen may serve as a valuable marker of distant organ injury in patients with skin burn.
Gross
M A
MA
Department of Surgery, University of Colorado Health Center, Denver 80262.
Viders
D E
DE
Brown
J M
JM
Mulvin
D W
DW
Miles
R H
RH
Brentlinger
E R
ER
Velasco
S E
SE
Crawford
T S
TS
Burton
L K
LK
Repine
J E
JE
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D000941:Antigens / Q000032:analysis*; D002056:Burns / Q000097:blood / Q000276:immunology / Q000473:pathology*; D002199:Capillary Permeability / Q000187:drug effects; D004727:Endothelium / Q000276:immunology / Q000473:pathology; D005167:Factor VII / Q000032:analysis / Q000276:immunology*; D007668:Kidney / Q000276:immunology / Q000473:pathology*; D008168:Lung / Q000276:immunology / Q000473:pathology*; D008297:Male; D009994:Osmolar Concentration; D011652:Pulmonary Circulation / Q000187:drug effects; D051381:Rats; D012867:Skin / Q000293:injuries*; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D014841:von Willebrand Factor / Q000276:immunology
D000941:Antigens; C031500:factor VII related antigen; D014841:von Willebrand Factor; D000493:Allopurinol; C038983:1,3-dimethylthiourea; D005167:Factor VII; D013890:Thiourea