Systemic sclerosis (SSc) is a generalized autoimmune disorder characterized by immunological abnormalities, microvascular dysfunction, and tissue fibrosis. This study evaluated the inflammatory processes occurring in skin of 7 patients with SSc of recent onset (average disease duration of 10 ± 3 months) to assess the involvement of monocytes/macrophages during the early stages of SSc. All SSc skin biopsies displayed inflammatory microvascular endothelial cell activation and fibrosis. Increased numbers of infiltrating inflammatory leukocytes were present in affected skin of recent onset SSc (p& < 0.01) mainly consisting of CD14-positive monocytes/macrophages (p& < 0.02). CD3 T lymphocytes were only slightly elevated in SSc skin (84 ± 39) compared to normal (51 ± 12), but the differences were statistically not significant. The ratio of CD14/CD3 cells was substantially higher in affected skin of recent onset SSc (4.0 ± 2.0) than in normal skin (1.4 ± 0.5, p& <0.01). Monocytes/ macrophages, therefore, are the predominant infiltrating mononuclear cell in skin lesions of recent-onset SSc. These results strongly suggest that CD 14-positive monocytes/macrophages play an important role during the early stages of SSc pathogenesis.
Objective:Hemangioma is an endothelial cell tumor that grows rapidly during infancy and regresses slowly during childhood. However, little is known about the natural history of this common tumor. To gain insight into the cellular mechanisms that underlie the switch from uncontrolled growth to involution of endothelium, we investigated the extent of cellular apoptosis versus proliferation in hemangioma specimens that spanned the natural life cycle of the tumor. Methods: We analyzed apoptosis and cellular proliferation in frozen sections from 16 hemangioma specimens using the TUNEL assay to detect apoptotic cells and the Ki67 antigen to detect dividing cells. Results: Apoptosis was low in proliferative phase hemangiomas but increased fivefold in involutive phase specimens obtained from children one to four years of age. Immunofluorescence double-labeling experiments showed that at least one third of the apoptotic cells were endothelial. As expected, cellular proliferation was high in specimens up to 2 years of age but decreased significantly thereafter. Apoptosis was consistently low in nine normal skin tissues (newborn to 4 years of age) obtained from discarded pathology specimens. Conclusions: These results suggest that increased apoptosis during the second year of life can offset cellular proliferation and may be involved in initiating regression of hemangioma.
These results suggest that increased apoptosis during the second year of life can offset cellular proliferation and may be involved in initiating regression of hemangioma.
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