Hr. Higley et al., EXTRAVASATION OF MACROMOLECULES AND POSSIBLE TRAPPING OF TRANSFORMINGGROWTH-FACTOR-BETA IN VENOUS ULCERATION, British journal of dermatology, 132(1), 1995, pp. 79-85
The pathogenesis of venous ulceration is thought to involve formation
of pericapillary fibrin cuffs as a result of venous hypertension, and
a recent hypothesis suggests that extravasated plasma proteins may bin
d or trap growth factors. We have compared the tissue distribution of
fibrin cuffs, plasma proteins, procollagen, and transforming growth fa
ctors (TGF-beta 1 and TGF-beta 2) within venous ulcers and normally he
aling graft donor sites. In venous ulcers, the papillary dermis and th
e ulcer bed contained convoluted capillaries with phosphotungstic acid
haematoxylin-positive pericapillary fibrin cuffs. By immunohistochemi
cal staining, the cuffs were positive for actin, and contained massive
ly redundant lamellae of basement membrane material which stained posi
tive for type IV collagen. Extravasated factor XIIIa and alpha(2)-macr
oglobulin were present within the fibrin cuffs. Increased numbers of t
ype I procollagen positive fibroblasts, and increased TGF-beta 1 immun
oreactivity were present within the fibrin cuffs, but not in the provi
sional matrix in the ulcer bed around the cuffs. In contrast, in norma
lly healing graft donor sites, tortuous capillaries and fibrin cuffs w
ere absent, factor XIIIa and alpha(1)-macroglobulin were restricted to
the lumina of vessels, and procollagen and TGF-beta immunoreactivity
were present within the granulation tissue and adjacent dermal matrix
at the wound margin. These observations suggest that growth factors cr
itical in wound healing, such as TGF-beta, are present within venous u
lcers, but are abnormally distributed. Their distribution within fibri
n cuffs and co-localization with extravasated plasma proteins, particu
larly alpha(2)-macroglobulin, which is a recognized scavenger molecule
for TGF-beta and other growth factors, provides evidence for a possib
le 'trapping' of growth factors in venous ulcers.