Insulin-like growth factors (IGFs) and IGF-binding proteins in human skin interstitial fluid.
Despite extensive investigation of the insulin-like growth factor (IGF)/IGF-binding protein (IGFBP) system in the circulation and body fluids, there is no information on this in interstitial fluid. We have compared the IGF/IGFBP system in the circulation with that in fluid obtained from blisters artificially raised by negative pressure in 10 healthy volunteers. IGFBP-1, -2, -3, and -4 were all found in blister fluid, but in concentrations much lower than those in matched serum. The IGF-I, IGF-II, and IGFBP-3 levels measured by RIA were 18%, 14%, and 16% of those in serum, respectively. Fast protein liquid chromoatography showed that both IGF-I and IGFBP-3 in 150- and 50-kilodalton complexes were approximately 13% and 37%, respectively, of the corresponding peaks found in matched serum. Compared to that in serum, the IGFBP-3 in the blister fluid was predominantly in a modified 29-kilodalton form, and there was increased activity of an IGFBP-3 protease. Therefore, although IGF concentrations are much lower in interstitial fluid than in the circulation, a greater proportion of this IGF is in forms more readily available for interaction with tissue receptors. The blister fluid appears to represent physiological interstitial fluid and may provide a model for studying the physiology and pathophysiology of growth factors in the interstitial environment.
Xu
S
S
Department of Medicine, University of Bristol, Bristol Royal Infirmary, United Kingdom.
Cwyfan-Hughes
S C
SC
van der Stappen
J W
JW
Sansom
J
J
Burton
J L
JL
Donnelly
M
M
Holly
J M
JM
D001768:Blister; D015153:Blotting, Western; D002850:Chromatography, Gel; D004591:Electrophoresis, Polyacrylamide Gel; D010450:Endopeptidases / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism*; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000032:analysis; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000032:analysis; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000032:analysis; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000032:analysis; D018969:Insulin-Like Growth Factor Binding Proteins / Q000032:analysis* / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007335:Insulin-Like Growth Factor II / Q000032:analysis; D011312:Pressure; D011863:Radioimmunoassay; D012867:Skin / Q000378:metabolism*
D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D018974:Insulin-Like Growth Factor Binding Protein 4; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D010450:Endopeptidases; C080473:insulin-like growth factor binding protein-3 protease