Inflammatory cell subpopulations in keloid scars

Boyce, Dean E.; Ciampolini, Jacopo; Ruge, Fiona; Harding, Keith; Murison, Maxwell M.S.C.

doi:10.1054/bjps.2001.3638

Cited by 86 publications

(102 citation statements)

References 23 publications

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“…Majority of keloid cases in our study show moderate amount of inflammatory cell infiltration (63%) around perivascular location composed mainly of lymphocytes which was similar to findings studied by Borgognoni et al, Blackburn et al and Boyce DE et al [10][11][12] No significant association was found between VEGFR-2 expression and amount of Inflammatory cell infiltration in keloid in our study. 87.5% of keloid scar in our study demonstrated the presence of large, broad, glassy, eosinophilic focally fragmented and haphazardly arranged collagen complexes referred to as "keloid collagen."…”

Section: -9supporting

confidence: 90%

A Study on Molecular Biology and Pathology of Keloid

Dr.Sudha¹

2018

jmscr

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Section: -9supporting

confidence: 90%

A Study on Molecular Biology and Pathology of Keloid

Dr.Sudha¹

2018

jmscr

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“…However, prolonged inflammation is implicated in abnormal scar formation [34,35] and in the aetiology of keloid scars [36]. Thus, abrogating the M1 phenotype in wounds may decrease the development of scarring [37]. While the relationship between the ratios of M1 and M2 macrophages in human wounds and the presence of keloid scarring remains ambiguous, keloid scar tissue has been noted to have a higher number of M2 macrophages as well as increased numbers of T and B cells [38].…”

Section: Discussionmentioning

confidence: 99%

Selective M2 Macrophage Depletion Leads to Prolonged Inflammation in Surgical Wounds

Klinkert¹,

Whelan²,

Clover³

et al. 2017

Eur Surg Res

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Background: A prolonged inflammatory phase is seen in aberrant wound healing and in chronic wounds. Macrophages are central to wound healing. Distinct macrophage subtypes have differing roles both in initial inflammation and in later tissue repair. Broadly, these cells can be divided into M1 and M2 macrophages. M2 macrophage proliferation and differentiation is regulated by colony-stimulating factor 1 (CSF-1) signalling and can be blocked by GW2580, a competitive cFMS kinase inhibitor, thereby allowing for analysis of the effect of M2 blockade on progression of surgical wounds. Materials and Methods: Macrophage Fas-induced apoptosis (MaFIA) transgenic mice with a macrophage-specific promoter used to express green fluorescent protein (GFP) were used to allow for cell tracking. The animals were treated by oral gavage with GW2580. Surgical wounds were created and harvested after 2 weeks for analysis. Results: GW2580-treated mice had significantly more GFP+ cells in the surgical scar than vehicle-treated animals (GW2580, 68.0 ± 3.1%; vehicle, 42.8 ± 1.7%; p < 0.001), and GW2580 treatment depleted CD206+ M2 macrophages in the scar (GW2580, 1.4%; vehicle, 19.3%; p < 0.001). Treated animals showed significantly higher numbers of neutrophils (vehicle, 18.0%; GW2580, 51.3%; p < 0.01) and M1 macrophages (vehicle, 3.8%; GW2580, 12.8%; p < 0.01) in the scar compared to vehicle-treated animals. The total collagen content in the area of the scar was decreased in animals treated with GW2580 as compared to those treated with vehicle alone (GW2580, 67.1%; vehicle, 79.9%; p < 0.005). Conclusions: Depletion of M2 macrophages in surgical wounds via CSF-1 signalling blockade leads to persistent inflammation, with an increase in neutrophils and M1 macrophages and attenuated collagen deposition.

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“…Infiltrating leukocytes are an important feature of healing wound tissue, and PMNs, lymphocytes, and macrophages may be sources of transforming growth factor ␤ (TGF␤), a growth factor important in the activity of fibroblasts in healing wounds. [41][42][43][44][45][46] However, the role of leukocytes in wound healing is complex, and they may function both to promote or retard wound healing or scar formation, depending on the timing and circumstances related to a given injury. 41,43,44 Confirmation of a link between scarring and CD18 cytoplasmic domain function may be tested in transgenic mice expressing this patient's CD18 truncation.…”

Section: Discussionmentioning

confidence: 99%

Unique CD18 mutations involving a deletion in the extracellular stalk region and a major truncation of the cytoplasmic domain in a patient with leukocyte adhesion deficiency type 1

Hixson

Smith

Shurin

et al. 2004

Blood

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Two novel CD18 mutations were identified in a patient who was a compound heterozygote with type 1 leukocyte adhesion deficiency and whose phenotype was typical except that he exhibited hypertrophic scarring. A deletion of 36 nucleotides in exon 12 (1622del36) predicted the net loss of 12 amino acid (aa) residues in the third cysteine-rich repeat of the extracellular stalk region (mut-1). A nonsense mutation in exon 15 (2200G>T), predicted a 36-aa truncation of the cytoplasmic domain (mut-2). Lymphocyte functionassociated antigen 1 (LFA-1) and macrophage antigen-1 (Mac-1) containing the mut-1 ␤ 2 subunit were expressed at very low levels compared with wild-type (wt) ␤ 2 . Mac-1 and LFA-1 expression with the mut-2 ␤ 2 subunit were equivalent to results with wt ␤ 2 . Binding function of Mac-1 with mut-2 ␤ 2 was equivalent to that with wt ␤ 2 . However, binding function of LFA-1 with the mut-2 ␤ 2 subunit was reduced by 50% versus wt ␤ 2 . It was concluded that (1) the portion of the CD18 stalk region deleted in mut-1 is critical for ␤ 2 integrin heterodimer expression but the portion of the cytoplasmic domain truncated in mut-2 is not; and (2) IntroductionImportant insights related to the molecular mechanisms that determine ␤ 2 integrin structure and function have arisen from the study of naturally occurring mutations in the common ␤ 2 subunit of this integrin family. 1,2 A range of mutations in the CD18 gene have been identified in patients with leukocyte adhesion deficiency type 1 (LAD-1), including deletions, truncations, substitutions, frame shifts, and intronic mutations that result in abnormalities of the CD18 protein ranging from absence of protein product, deficient alpha-beta subunit association, and reduced protein size. 1,3-5 All such mutations have resulted in diminished expression of the CD18 integrins on leukocytes, and some mutations also have caused integrin dysfunction. 1,[3][4][5] Patients typically have recurrent bacterial or fungal infections of skin and mucous membranes, impaired mobilization of leukocytes to sites of infection, severe gingivitis/ periodontitis with permanent loss of dentition, and atrophic scarring of wounds. 1,2,6 Laboratory features include a pronounced leukocytosis in the absence of infection, reduced expression of all members of the CD18 or ␤ 2 integrin family on circulating leukocytes, and diminished CD18-dependent leukocyte functions, including cell adhesion, chemotaxis, transendothelial migration, and oxidative burst activation in response to iC3b-coated particles. 1,2,6 We have identified an adult male patient with LAD-1 whose clinical features resemble those of the moderate LAD-1 phenotype, except that his wounds heal with hypertrophic rather than atrophic scarring. His levels of CD18 integrin expression are higher than those of most other reported patients with the moderate phenotype of LAD-1, but the CD18-dependent functions of his leukocytes were similar to those of other moderate phenotype individuals. 1,7 He was found to be a compound heterozygote with 2 novel m...

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Inflammatory cell subpopulations in keloid scars

Cited by 86 publications

References 23 publications

A Study on Molecular Biology and Pathology of Keloid

A Study on Molecular Biology and Pathology of Keloid

Selective M2 Macrophage Depletion Leads to Prolonged Inflammation in Surgical Wounds

Unique CD18 mutations involving a deletion in the extracellular stalk region and a major truncation of the cytoplasmic domain in a patient with leukocyte adhesion deficiency type 1

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