Decreased levels of alpha 1(I) procollagen mRNA in dermal fibroblasts grown on fibrin gels and in response to fibrinopeptide B.

We have investigated human neonatal fibroblast synthetic activity in response to fibrin substrates and components of fibrin formation and degradation. Greater than threefold downregulation of procollagen mRNA levels was seen 24 hours after fibroblasts were grown on fibrin gels as compared to tissue culture plastic. This downregulation occurred in both reptilase-generated fibrin (retention of fibrinopeptide B) and thrombin-generated fibrin (loss of both fibrinopeptide A and B). However, fibroblasts grown on fibrin retained their capacity to respond to the stimulatory action of transforming growth factor (TGF)-beta 1. Fibroblasts seeded on reptilase-generated fibrin displayed an abnormal morphology manifested by dendritic appearance and cell rounding, while fibroblast attachment was enhanced by 30% on thrombin-generated fibrin substrate (P < 0.02). Fibrinopeptides A and B, which are generated during fibrin formation, increased and decreased procollagen mRNA levels, respectively. Tissue plasminogen activator (t-PA) increased procollagen mRNA and TGF-beta 1 levels as early as 6 hours after cells were grown on tissue culture plastic, but this stimulation did not occur in cells cultured on a fibrin substrate. We conclude that alpha 1(I) procollagen mRNA levels in cultures of human dermal fibroblasts are consistently down-regulated by a fibrin substrate and are directly and profoundly influenced by complex interactions between components involved in the formation and removal of fibrin.

Low oxygen tension decreases receptor binding of peptide growth factors in dermal fibroblast cultures.

We have investigated receptor binding of epidermal growth factor (EGF) and transforming growth factor-beta 1 (TGF-beta) in cultures of human dermal fibroblasts exposed to low (2%, hypoxia) or standard (20%) oxygen tension. Compared to standard oxygen, the binding of both 125I-TGF-beta and 125I-EGF in low oxygen tension was diminished by a mean of 65 and 62%, respectively (P < 0.02), and was reversed by reexposure of cultures to standard oxygen tension. Low oxygen tension decreased the number of binding sites of both EGF (mean = 44%) and TGF-beta (mean = 33%). Preincubation of the media in the two different oxygen conditions showed that alterations in the redox potential of the medium was not responsible for the changes observed in receptor binding. As shown by Northern analysis, diminished TGF-beta receptor binding in hypoxia was accompanied by up to a 10-fold decrease in mRNA levels of TGF-beta type II receptor. We conclude that low oxygen tension decreases EGF and TGF-beta receptor binding and synthesis.

Adverse sequelae of venous hypertension.

Venous hypertension and venous ulcers are clinical entities that are expected to increase as the population ages. This article will review the current clinical and laboratory data pertinent to lipodermatosclerosis and venous ulcer development. An understanding of these putative pathophysiologic mechanisms may help the clinician to better diagnose and manage such patients.

The clinical spectrum of lipodermatosclerosis.

Lipodermatosclerosis refers to the skin induration and hyperpigmentation of the legs that often occurs in patients who have venous insufficiency. Lipodermatosclerosis has also been termed hypodermitis sclerodermiformis and appears to be similar if not-identical to the recently described sclerosing panniculitis of the leg. There has been much confusion about the nature, clinical course, and treatment of lipodermatosclerosis. We believe that lipodermatosclerosis has an acute, inflammatory phase and a chronic, fibrotic stage, although a spectrum exists. Direct immunofluorescence studies of early and late lesions are helpful in that they show dermal pericapillary fibrin deposits without other immunoreactants. Treatment of lipodermatosclerosis consists of compression therapy with either graded stockings or elastic bandages. We and others have found that the anabolic steroid stanozolol improves this condition rapidly and consistently.

Solitary fibrosing paraspinal plaque: solitary morphoea profunda?

Solitary morphoea profunda is a recently described morphological variant of localized scleroderma. Two of the five reported patients had a solitary fibrotic plaque in the paraspinal region. We report a 16-year-old boy with a solitary fibrotic paraspinal plaque which, on histological examination, showed dermal and subcutaneous sclerosis, with a polymorphous infiltrate including plasma cells and eosinophils. Laboratory tests were either negative or normal, except for mild peripheral blood eosinophilia. Antinuclear antibodies were not detected, and the patient had no evidence of Borrelia infection. Magnetic resonance imaging (MRI) showed that the process involved the subcutaneous tissue, but did not extend to the underlying bone. As half of the patients with this entity (three of six) now described have had a solitary fibrotic plaque in a paraspinal location, we suggest that it may be premature to classify all these cases as being a variant of morphoea. We propose the use of the descriptive term solitary fibrosing paraspinal plaque, until the aetiology or aetiologies of this condition are better understood.