The mechanisms underlying the pathogenesis of keloids have not been fully characterized despite extensive past and present research. Results of past and present studies have shown that the immune system is actively involved in the development of these lesions. Future investigations into the biochemistry and immunologic factors of keloids are anticipated and expected to produce additional insight. The inability to identify cellular (fibroblast) abnormalities has led most investigators to focus on the humoral regulators of wound healing, that is, biochemical substances, immunologic mediators and growth factors. Future studies are needed to confirm or refute the presence of AFA. AFA, if they exist, may prove to be useful as immunologic markers of keloids and may help distinguish keloids from hypertrophic scar in the early stages of wound healing. The influence of immunologic mediators may be more impressive early in the development of scars. "Young" or "early" is defined as less than two years of age, whereas "old" or "late" keloids are more than two years of age. We suggest that future studies stratify keloids into early versus late and also measure the rates of collagen synthesis of fibroblasts derived from the normal and abnormal specimens from the same patient. Analysis of the leukocyte factors will clarify the role the immune system has in the regulation of collagen synthesis. Preliminary investigations have shown that immunotherapy may be of value in the treatment of keloids. The role of fibroblast heterogeneity needs to be investigated. It is not known which aspects of fibroblast heterogeneity are responsible for the localized and accelerated rates of collagen synthesis of keloid fibroblasts.
"When keloids were treated with intralesional cryotherapy, improvement of the lesions was correlated with decreased numbers of MCs, as assessed histochemically (Har-Shai et al., 2011). Histamine levels were elevated in keloid lesions which may lead to the abnormal collagen crosslinking seen in such pathology (Placik & Lewis, 1992). Nevertheless, the primary mediators exocytosed from cutaneous MCs that promote keloid development have not been identified. "
[Show abstract][Hide abstract] ABSTRACT: Mast cells (MCs) are active participants in blood coagulation and innate and acquired immunity. This review focuses on the development of mouse and human MCs, as well as the involvement of their granule serine proteases in inflammation and the connective tissue remodeling that occurs during the different phases of the healing process of wounded skin and other organs. The accumulated data suggest that MCs, their tryptases, and their chymases play important roles in tissue repair. While MCs initially promote healing, they can be detrimental if they are chronically stimulated or if too many MCs become activated at the same time. The possibility that MCs and their granule serine proteases contribute to the formation of keloid and hypertrophic scars makes them potential targets for therapeutic intervention in the repair of damaged skin.
Advances in Immunology 02/2014; 122:211-52. DOI:10.1016/B978-0-12-800267-4.00006-7 · 5.96 Impact Factor
"Aside from the correlation that fibrosis at wounds only commences at late embryonic stages, after these leukocytic lineages have been born and are robustly recruited to sites of tissue damage, there are other clues that various components of the inflammatory response might be in part responsible for fibrosis at the wound site. For example, several correlative studies have indicated links between numbers of T cells and Langerhans cells in the skin, and the resulting formation of hypertrophic or keloid scars (Placik and Lewis, 1992; Castagnoli et al., 1997; Niessen et al., 2004) and mast cells has been implicated also because of association between increased IgE levels and frequency of allergic symptoms in patients with excessive scarring (Smith et al., 1997; Gruber, 2003). There is considerable anecdotal clinical evidence indicating that elderly patients suffer much less extensive hypertrophic scarring than younger individuals (A McGrouther, Manchester , personal communication). "
[Show abstract][Hide abstract] ABSTRACT: The healing of a skin wound is a complex process involving many cell lineages. In adult tissues, repair is always accompanied by a robust inflammatory response, which is necessary to counter the potential for infection at any site where the skin barrier is breached. Unlike embryonic tissues that can repair perfectly without a remnant scar at the wound site, adult tissue repair always leads to formation of a fibrotic scar where the wound has healed. In recent years, it has become clear that the wound inflammatory response may be, at least in part, responsible for fibrosis at sites of tissue repair. In this review, we consider the beneficial vs the detrimental functions of inflammatory cells during the repair response and compare data from other tissues, the lung, and liver, where fibrosis and its resolution may be related to a damage-triggered inflammatory response. We also consider how it may be possible to molecularly disentangle the potentially good from the bad influences of inflammatory cells during tissue repair and how fundamental studies in inflammatory cell biology may prove the way forward for development of drug targets in this respect.
[Show abstract][Hide abstract] ABSTRACT: Further attempts to achieve a clinical distinction between hypertrophic and keloid scars seem pointless. Research in recent years has shifted from the extracellular components towards the cells themselves. Much more work needs to be done to characterise the activities of the various cell lines and the mechanisms of their control. A key question is whether the cells are due to a different subpopulation of fibroblasts or whether they are normal wound-healing cells acting under some chemical or physical influence. Ultimately, most hypertrophic and keloid scars become flat and pale, although the time sequence is very variable and there is little understanding of the process of scar maturation. Meanwhile, the problem remains as a significant cause of human suffering deserving further investment of time and resources.
Katarzyna Wawrzyniec, Aleksandra Kawczyk-Krupka, Zenon P Czuba, Wojciech Król, Aleksander Sieroń
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