The purpose of this study was to determine the frequency, distribution, and nature of cellular infiltrates in 108 skin biopsies from patients with systemic scleroderma (SS) and localized scleroderma (LS). Cellular infiltrates, perivascular or diffuse, were noted in 49% of SS and 84% of LS patients and consisted of lymphocytes, plasma cells, and macrophages. No correlation was noted between the presence or severity of skin cellular infiltrates and serum serologic abnormalities.Systemic scleroderma is a connective tissue disease that affects various organ systems, but particularly the skin, lungs, gastrointestinal tract, and kidneys. Localized scleroderma affects only the skin, and it is not presently known whether it represents a separate entity or whether it is a clinical variant of systemic scleroderma. The pathogenesis of scleroderma remains unknown, although current research implicates three pos-

There is some evidence that type I and type III collagens may be present in the same fibril. In order to demonstrate this, double labeling immunofluorescence microscopy and immunoelectron microscopy were performed with antibodies directed against the collagen molecule and the aminopropeptide domains of type I and type III procollagens using embryonic (postabortion) and adult human skin. Double indirect and protein A immunoelectron microscopy were carried out with 5- and 15-nm gold particles. Skin extracts were also studied by immunoblotting. Double immunofluorescence microscopy with antibodies against type I and type III collagen molecules revealed patterns of fluorescence that were identical in both fetal and adult skins. Immunofluorescence microscopy using an antibody directed against the aminopropeptide of type III procollagen labeled the entire dermis in both embryonic and adult skins. In contrast, although the aminopropeptide of type I procollagen was present throughout embryonic dermis, it was markedly reduced in adult dermis, except for the epidermo-dermal junction. Double immunoelectron microscopy of fetal skin revealed labeling of the aminopropeptide of type I and type III procollagens on the same thin (20-30 nm) fibrils. Large type I fibrils (90-100 nm) were coated with type III collagen molecules and their corresponding aminopropeptide but not with the aminopropeptide of type I procollagen. The aminopropeptide of type I procollagen was present on thin fibrils only at the epidermo-dermal junction in adult skin. Immunoblotting of skin extracts revealed the presence of both pN-type III procollagen (collagen plus the aminopropeptide) and pN-type I procollagen in fetal skin, but only pN-type III in adult skin. This study demonstrates that type I and type III collagens coexist within the same fibril and that the aminopropeptide of type III procollagen is present at the surface of type I collagen fibrils that apparently have reached full growth.

Human skin was labeled with purified antibodies against type I and m collagens and against their extension aminopropeptides by using the ferritin technique. Both aminopropeptides were visualized mainly along thin collagenous fibrils (diameter, 20-40 nm) and rarely in nonfibrillar regions of the skin. The labeling showed a periodicity of 60-65 nm resembling the D (67 nm) stagger of collagen molecules. Blocking of antibodies with aminopropeptides and treatment of tissues with procollagen NH2-terminal protease abolished labeling. Antibodies against type I collagen uniformly labeled -80% of the fibrils (diameter, 20-80 nm), while reaction with antibodies against type m collagen was restricted to thin fibrils. It is currently thought that the aminopropeptides of procollagen molecules are cleaved after they are released from the cell and before fibril formation. Our data indicate that aminopropeptides are removed at the fibrillar level and that fibril growth can be regulated by extracellular procollagen processing. Type I and III collagens are major components of the dermis and are organized into fibrils varying considerably in diameter. Distinct growth of fibrils is observed during development and may be disturbed in certain skin diseases (1). The mechanism of controlling this process is unknown. It has also not been established whether type I and III collagens are present in the same fibrils. Both collagens can form D-staggered fibrils in vitro showing identical cross-striations when examined in the electron microscope (2). Because specific antibodies against various collagens and procollagens are available (3, 4), it is feasible to identify distinct types of collagenous proteins at the ultrastructural level in situ, as was recently done for type III collagen (5).Interstitial collagens are synthesized in the form of procollagens that possess additional extension amino-and carboxypropeptides. Each precursor-specific peptide is removed by specific proteases (procollagen NH2-terminal and COOH-terminal proteases) presumably after release of procollagens from the cell (6). Cell and organ culture studies indicated different kinetics in the processing of type I and III procollagens (7-9). After cleavage, the aminopropeptides persist for some time in the extracellular space, as shown by immunofluorescence staining with antibodies against these peptides (3, 4).A functional role for extension aminopropeptides in the control of fibril growth was first suggested in studies of dermatosparactic animals, which, due to a defective NH2-terminal protease, accumulate an intermediate form of type I procollagen (pN-collagen) in the skin and other organs (10, 11). The collagenous fibrils appeared thin and hieroglyphic (12, 13) and could be stained with antibodies against the aminopropeptide by using a ferritin label (13). Small amounts of type I and III pN-collagens could also be extracted from the skin of growing animals (14-18). It was suggested (3, 14, 19) that these aminopropeptides are structural elements ofimmature or th...

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The major histological characteristic of sun-damaged skin is the accumulation of an elastotic material that appears to replace collagen. This elastotic material consists primarily of elastin and histological studies suggest a large loss of collagen in the dermis of chronically sun-damaged skin. In this study, we examine the content and distribution of collagen and procollagen in sun-damaged human skin. The total collagen content of sun-damaged skin was 20% less than nonsolar-exposed skin (524 micrograms collagen per mg total protein in sun-damaged skin and 667 micrograms collagen per mg total protein in nonsolar-exposed skin). In addition, there was a 40% decrease in the content of intact amino propeptide moiety of type III procollagen in sun-damaged skin (0.68 U per 50 mg wet weight) as compared to nonsolar-exposed skin (1.12 U per 50 mg wet weight). The data suggest that this change in collagen content is due to increased degradation. The distribution of collagen in sun-damaged skin was examined by indirect immunofluorescence. Mild digestion of sun-damaged skin with elastase removed the elastin and revealed the presence of collagen in the elastotic material. Therefore, the elastin appears to mask the presence of collagen fibers in the dermis of sun-damaged skin.