EUROPEAN TISSUE REPAIR SOCIETY
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EUROPEAN TISSUE REPAIR SOCIETY SCAR CONTROL III |
THE ELASTIC SYSTEM IN HYPERTROPHIC SCARS AND KELOIDSTP Amadeu, A Braune, LC Porto, A Desmoulière and AMA CostaWOUND healing is a complex series of events that involves many cellular types, soluble mediators and extracellular matrix components in response to tissue injury. It takes place in three phases: inflammation, granulation tissue formation and tissue remodelling. However, in cutaneous wound healing, there are situations in which this mechanism does not occur harmoniously and abnormal scars, such as hypertrophic scars and keloids are formed. Hypertrophic scars and keloids are two kinds of excessive cutaneous scarring characterized by increased extracellular matrix deposition. According to Linares1 hypertrophic scars are painful lesions that rise above the skin surface, presenting redness and itching, but are limited to the border of the injury; these lesions are frequently associated with contractures. Keloids are abnormal scars, variably pruritic and painful, which are not limited to the borders of the initial injury.2 Hypertrophic scars are characterized by an accumulation of myofibroblasts expressing á-smooth muscle actin and thin, randomly organized, collagen fibres, both usually arranged in nodules.3–5 In keloids myofibroblasts, expressing á-smooth muscle actin, are usually absent, the cellularity is less marked and the collagen bundles are thicker than in hypertrophic scars.3–5 Elastic systemThe elastic system is present in many tissues as a network which is responsible for the physiological elasticity of the organs. In pathological conditions, such as fibrosis, a larger amount of elastic tissue is present.6–8 The components of the elastic system are fibrillin-rich microfibrils and elastin; fibrillin-rich microfibrils may be observed alone, but elastin is always associated with a pre-formed template of microfibrils. Based on histochemical observations the elastic system fibres have been classified in three types: oxytalan, elaunin and elastic fibres. Oxytalan fibres are formed exclusively by microfibrils (10–12 nm in diameter), while elaunin fibres are formed by microfibrils and small amounts of elastin; elastic fibres are also formed by microfibrils and elastin, but with a proportionately larger amount of elastin. 9 In normal skin, oxytalan fibres are very thin and directed perpendicularly to the epidermal basement membrane in a candelabra-like arrangement; elaunin fibres are thicker and are organised mainly parallel to the epidermis, forming a plexus that interconnects oxytalan fibres with elastic fibres localised in reticular dermis.9,10 The elastic system in wound healingThe elastic system fibres are rarely considered in cutaneous wound healing studies and contradictory data about their distribution during the wound healing process are present in the literature. Some older studies, using histochemical methods, reported the absence of elastic system fibres in scars or their presence only in the late phases of cutaneous wound healing.11 However, more recent reports have shown that elastic system components are present in the early phases of cutaneous wound healing,12–14 showing that elastic system fibres are replaced and, as with many other components of the extracellular matrix, should have a role during cutaneous wound healing. The elastic system in hypertrophic scars and keloidsOnly a few studies have shown the distribution of elastic system components in normal mature scars, keloids or hypertrophic scars.10,15,16 These used mainly histochemical techniques. In hypertrophic scars the clinical improvement occurs concomitantly with the rearrangement of the elastic system components.10 Therefore it would be of interest to use more specific techniques to characterise the organisation of the elastic system components in hypertrophic scars and keloids. In this present study the distribution of the elastic system components, fibrillin-1 and elastin, was studied using immunohistochemistry. Hypertrophic scars (n = 5) (four men, aged from 16 to 31 years), keloids (n = 5) (three men, aged from 18 to 61 years) and normal skins (n = 5) (two men, aged from 22 to 37 years) were collected during reconstructive surgery. The classification of hypertrophic scars and keloids was based on clinical criteria. The Ethical Committee of the University Hospital of the State University of Rio de Janeiro approved this study and all patients enrolled gave informed and written consent. The fragments were formol-fixed and paraffin-embedded. 
Figure 1: Fibrillin-1 and elastin immunolabelling in normal skin, hypertrophic scar and keloid. In normal skin fibrillin is arranged in a candelabra-like pattern in the papillary dermis (a); in hypertrophic scar the arrangement is disturbed and the amount of fibrillin-1 reduced (c); in keloids only scarce fibres of fibrillin-1 are present (arrows) (e). In normal skin elastin is observed in short fibres intermingled with collagen fibres (b), in hypertrophic scar elastin is not observed within nodules (*), but is observed around the nodules (arrows) (d); in keloids many fibres containing elastin are observed, arranged parallel to the epidermis (f). Original magnification: a, c and e, 180x; b, d and f, 370x. In this immunohistochemistry study, endogenous peroxidase was blocked, and sections were incubated with the mouse monoclonal primary antibodies, anti-human fibrillin-1 (Chemicon, Temecula, CA) or anti-human elastin (Sigma, St Louis, MO). For revelation, the Envision system® (DAKO, Carpinteria, CA) was used, with diaminobenzidine as chromogen, and the nuclei were stained with haematoxylin. Negative controls were performed by replacing the primary antibody by non-immune serum and no labelling was observed. In normal skin, fibrillin-1 was observed in thin oxytalan fibres in the papillary dermis arranged perpendicularly to the epidermis in a typical candelabra-like arrangement, in the thicker elaunin fibres parallel to the epidermis, and also in the reticular dermis around cutaneous appendages and vessels (Figure 1a). Thick fibres containing elastin (elaunin and elastic fibres) were observed mainly in the reticular dermis (Figure 1b), but were sometimes absent around cutaneous appendages and vessels. In hypertrophic scars the arrangement of both fibrillin-1 and elastin was disturbed. In the superficial dermis there was a decrease in the amount of both fibrillin-1 and elastin and the candelabra- like pattern of fibrillin-1 was absent (Figure 1c), while in the deep dermis, fibres were fragmented. In the nodules of hypertrophic scars elastin was present only in small deposits (Figure 1d). The organization of the elastic system was also disturbed in keloids. In the papillary dermis fibrillin- 1 deposition was decreased and the candelabra-like pattern of fibrillin-1 was absent (Figure 1e). In the deep dermis, fibrillin-1 deposition was decreased while elastin deposition was increased (Figure 1f) and the elastin was present in fibres orientated parallel to collagen fibres. In this study it was shown that there is a disturbance in the organisation of the elastic system fibres in both hypertrophic scars and keloids compared to normal skin. Furthermore there is a difference between hypertrophic scars, which showed a decrease in elastin in the deep dermis, and keloids, which showed a marked increase in elastin in the same region. The role of these components in normal cutaneous would healing remains to be elucidated, and further studies are necessary to establish whether alterations in the expression of the elastic system components are a cause or a consequence of excessive scarring. References
T.P. Amadeu, A. Braune, L.C. Porto and A.M.A. Costa Corresponding author: |
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Bulletin 12.1 & 2 Contents |
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