Skin biopsies demonstrate site-specific endothelial activation in mouse models of sepsis.
OBJECTIVE
Skin biopsies allow for direct phenotyping of the endothelium in clinical settings.


OBJECTIVE
We hypothesize that in murine sepsis endothelial activation is manifested by changes in protein and mRNA expression in skin biopsies, and that such alterations differ from other organs.


METHODS
In two mouse models of sepsis [endotoxemia and cecal ligation puncture (CLP)], we measured circulating levels of endothelial biomarkers, quantitated mRNA expression of activation markers and assayed for protein expression using immunohistochemistry.


RESULTS
Endotoxemic mice demonstrated increased circulating levels of sE-selectin, sICAM-1, sVCAM-1 and sP-selectin at 24 h, while CLP was associated with increased levels of sE-selectin alone. In real-time PCR, mRNA levels for P-selectin, ICAM-1 and PAI-1 were increased in skin from endotoxemic mice. In CLP, mRNA levels for P-selectin, ICAM-1, E-selectin and PAI-1 were elevated, while VCAM-1 expression was reduced in skin. Most, but not all of these changes correlated with alterations in immunohistochemical staining. Expression patterns in skin differed from those in brain, heart, and lung.


CONCLUSIONS
Skin biopsies demonstrated endothelial cell activation during sepsis. The expression patterns differed by type of sepsis model and between vascular beds of skin, brain, heart, and lung, providing a foundation for identifying skin microvascular-bed-specific molecule signatures.
Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, Mass. 02215, USA. nshapiro@bidmc.harvard.edu
Nathan I
NI
Shapiro
Kiichiro
K
Yano
Midori
M
Sorasaki
Chris
C
Fischer
Shou-Ching
SC
Shih
William C
WC
Aird
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D002432:Cecum / Q000473:pathology; D020405:Dermis / Q000098:blood supply* / Q000473:pathology*; D004195:Disease Models, Animal; D019040:E-Selectin / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000473:pathology* / Q000502:physiology; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D008026:Ligation; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019007:P-Selectin / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018805:Sepsis / Q000473:pathology*; D058258:Serpin E2; D015843:Serpins / Q000235:genetics / Q000378:metabolism; D012995:Solubility; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D014951:Wounds, Stab
D015415:Biomarkers; D019040:E-Selectin; D008070:Lipopolysaccharides; D019007:P-Selectin; D012333:RNA, Messenger; D058258:Serpin E2; C511869:Serpine2 protein, mouse; D015843:Serpins; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1