Retention of clostridial collagenase by primary cultures of parenchymal cells prepared from adult rat liver.
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Biomedical subjects
Publications and source records attributed to R F Diegelmann.
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Fibroblasts were isolated from keloid, normal skin, and normal scar and maintained in tissue culture for four passages. Growth kinetics were the same for all groups on days 2 through 12. However, the rate of collagen synthesis per fibroblast was greater in keloid derived cells than any controls at all growth phases. Keloid fibroblasts have an autonomous capacity to synthesize collagen at a significantly increased level in vitro, which may explain in part why these lesions are characterized by increased collagen deposition.
The events of wound healing are defined as collagen metabolism, epithelialization, and contraction. Recent findings that further our understanding of these pheneomena are presented and correlated with the important clinical problems confronting plastic surgeons. The future direction of wound healing investigation and its application to practical surgical care are predicted.
The increased collagen synthesis and deposition, which is characteristic of keloids, may be related to an immune response initiated by wounding. Therefore, we examined various systemic and localized immune parameters in keloid patients to establish if such factors are related to keloid pathogenesis. To determine if there is a systemic immune response, we compared the serum levels of IgG and IgM in keloid patients to those in a closely matched population. In addition, we measured complement levels (Clq, C3, and C4) and receptors for sheep (E), mouse erythrocytes (MRBC), and complement (EAC) on blood lymphocytes. All of these were in the normal range in the keloid patients. However, the extractable IgG from keloid tissue was significantly increased (compared to normal skin and normal scar controls), suggesting a localized immune response. To determine whether keloid formation is associated with a specific histocompatibility locus, human lymphocyte antigen (HLA) profiles of 45 keloid patients were analyzed; no significant differences in the incidence of HLA-A and B antigens were found (compared to 200 controls). These studies suggest that there is a localized immune response involved in keloid pathogenesis, one which is not related to either the HLA-A or B histocompatibility loci.
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Collagen synthesis is increased over three-fold in capsules surrounding dimethylbenzanthracene-induced rat breast tumors compared to the tumor parenchyma and over six-fold compared to normal breast connective tissue. Increased collagen synthesis is independent of the rate of tumor growth and final tumor size. Pretreatment of animals with beta-aminopropionitrile to inhibit collagen cross-linking caused an 82% decrease in tumor formation and a significant reduction in tumor volume (approximately 0.4 cu cm) compared to controls (approximately 10 cu cm). The four small tumors that did develop in the lathyritic animals had increased collagen synthesis in the interior tumor stroma and reduced collagen synthesis in the tumor capsule. These findings suggest that the collagenous capsule surrounding dimethylbenzanthracene tumors functions as a physical barrier to protect the tumor from the immune system of the host. The apparent antitumor effects of beta-aminopropionitrile may be due to immunopotentiation and/or cytotoxic actions of the drug.
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The deposition of alpha-1-antitrypsin and alpha-2-macroglobulin, both known to be inhibitors of human skin collagenase, is significantly increased in keloids and in hypertrophic scars (as compared to normal skin). However, following intralesional triamcinolone treatment, a marked resorption of these abnormal scars occurs along with a significant reduction of the alpha-1-antitrypsin deposits. These findings suggest that alpha-globulins are involved in abnormal scar formation, and that triamcinolone may remove collagenase and/or protease inhibitors--thereby allowing activation of the collagenase with subsequent breakdown and resorption of the excessive collagen.
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Contraction and epithelization are two phenomena of "wound healing" retarded by corticosteroids. It is unclear how these agents affect collagen synthesis and wound remodeling. The methods used by several authors to conclude that steroids inhibit collagen synthesis are questioned. Therefore, collagen synthesis was measured in cultured steroid-treated chick embryo calvaria, 5 day open wounds in treated rats, and intralesionally injected human keloids. Collagen synthesis was suppressed only by long-term administration of massive systemic doses of a sustained release form of methylprednisolone (Depo-Medrol). Large, intermittent doses of corticosteroids (triamcinolone and Solu-Medrol) did not alter collagen synthesis. Because human keloids become softer and smaller following intralesional administration of triamcinolone without lowering the normally high rate of collagen synthesis, we hypothesize that corticosteroids enhance collagen degradation.
A highly reactive biomaterial (clay) and a relatively nonreactive substance (silicone) were implanted separately in primarily closed incisions on the backs of rats. Collagen synthesis was determined in biopsies from each test site after 8 days. The biochemical measurements of collagen synthesis showed a significant correlation with the gross pathologic and histologic findings.
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