Immunohistochemical localization of collagen types I and VI in human skin wounds

Betz, P.; Nerlich, Andreas G.; Wilske, J.; Tübel, Jutta; Penning, R.; Eisenmenger, Wolfgang

doi:10.1007/bf01225021

Cited by 40 publications

(24 citation statements)

References 16 publications

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“…Wound age determination is closely involved in the pathophysiology of the wound healing process. With advances in biochemical and immunohistochemical techniques, several markers have been applied to wound age determination [3,4,5,6,7,8] and immunohistochemical analysis is now exclusively utilized for wound age determination [9,10,11,12,13,14,15,16,17,18,19,20,21]. VEGF has been characterized as an angiogenic growth factor from media conditioned by bovine pituitary folliculostellate cells.…”

Section: Discussionmentioning

confidence: 99%

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Forensic application of VEGF expression to skin wound age determination

et al. 2004

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An immunohistochemical study combined with morphometry was carried out to examine the time-dependent expression of vascular endothelial growth factor (VEGF) using 53 human skin wounds with different wound ages (groups I: 0-12 h, II: 1-4 days, III: 7-14 days and IV: 17-21 days). In the human wound specimens aged 4-12 h, neutrophils recruited at the wound showed no positive signals for VEGF. With an increase in wound ages of > or =7 days, granulation tissue and angiogenesis were observed, with the migration of macrophages and fibroblasts of which the cytoplasm expressed VEGF-positive reactions. Morphometrically, the average VEGF-positive ratio was highest in group III, followed by that of group IV. In groups III and IV, 13 out of 26 wound samples had VEGF-positive ratios of more than 50%. However, all of the wound samples in groups I and II showed VEGF-positive ratios of less than 50%. With regard to the practical applicability and forensic validity, these observations suggest that a VEGF-positive ratio of more than 50% possibly indicates a wound age of 7 days or more.

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Section: Discussionmentioning

confidence: 99%

“…Thus, many studies on forensic wound age determination have been performed [3,4,5,6,7,8,9,10]. Recently, biological substances such as growth factors, cytokines, and adhesion molecules have become useful markers for wound age determination [11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30].…”

Section: Introductionmentioning

confidence: 98%

Forensic application of VEGF expression to skin wound age determination

et al. 2004

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“…The recovery of IFP, on the other hand, requires both transcapillary and interstitial filtration as well as remodeling of the interstitium. Interstitial collagen synthesis and the remodeling of the 3-dimentional ECM structure may be slow processes as reported in wound healing (25) and require more time than the increase in vascular resistance.…”

Section: Discussionmentioning

confidence: 99%

Collagenase Increases the Transcapillary Pressure Gradient and Improves the Uptake and Distribution of Monoclonal Antibodies in Human Osteosarcoma Xenografts

Eikenes¹,

et al. 2004

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Cancer therapy based on tumor-selective macromolecules may fail due to the elevated interstitial fluid pressure (IFP) that reduces the transvascular and interstitial convection in solid tumors. Modulation of the tumor extracellular matrix (ECM) may reduce IFP and enhance transvascular filtration and interstitial transport of macromolecules. We therefore measured the effect of the ECM-degrading enzyme collagenase on IFP and microvascular pressure (MVP) in human osteosarcoma xenografts using the wick-in-needle and micropipette methods, respectively. The tumor uptake and distribution of a systemically administered osteosarcoma-associated monoclonal antibody (TP-3) after i.v. injection of collagenase were analyzed using confocal laser scanning microscopy. Collagenase (0.1%) reduced both IFP (45%) and MVP (60%), but the kinetics of the recoveries differed, because MVP had recovered by the time IFP reached its minimum level. Thus, collagenase increased the transcapillary pressure gradient, inducing a 2-fold increase in the tumor uptake and improving the distribution of the monoclonal antibody, which was localized further into the tumor. To study the mechanism of the reduction in MVP, mean arterial blood pressure was measured and found not to be affected by the collagenase treatment. The reduction in MVP was rather due to reduced vascular resistance because microvascular-associated collagen was totally or partially disintegrated. Although collagenase may favor metastasis and thus not be clinically relevant, this study shows proof of principle that degradation of the ECM leads to a favorable change in the transvascular pressure gradient, thereby increasing antibody penetration and binding to tumor cells.

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“…The molecular mechanisms of wound repair are not fully understood but involve growth factors, cytokines, adhesion molecules, and matrix metalloproteases [9][10][11][12][13]. Some of these substances have been used for the determination of wound age and wound vitality [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28].…”

Section: Introductionmentioning

confidence: 99%

Detection of fibrocytes in human skin wounds and its application for wound age determination

et al. 2009

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Fibrocytes, a newly identified cell type, are bone marrow-derived mesenchymal progenitors that coexpress hematopoietic cell antigens and fibroblast products. In this study, a double-color immunofluorescence analysis was carried out using anti-CD45 and anti-collagen type I antibodies to examine the time-dependent appearance of fibrocytes, using 53 human skin wounds with different wound ages (group I, 0-3 days; group II, 4-7 days; group III, 9-14 days; and group IV, 17-21 days). In wound specimens with an age of less than 3 days, CD45+/collagen type I+ fibrocytes were not detected. The fibrocytes were initially observed in wounds aged 4 days, and their number increased in lesions with advances in wound age. In a semiquantitative morphometrical analysis, the average number of fibrocytes was highest in the wounds of group III. These findings imply that human skin wounds containing fibrocytes are at least 4 days old. Moreover, a fibrocyte number of over 10 indicates a wound age between 9 and 14 days (i.e., group III). Based on the average number of fibrocytes in each group, a fibrocyte number of over 15 more strongly suggests a wound age of 9-14 days. Together, our observations indicate the participation of fibrocytes in wound healing of human skin inducing the accumulation of extracellular matrix components, and therefore, detection of fibrocytes could be a useful marker for wound age determination.

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Immunohistochemical localization of collagen types I and VI in human skin wounds

Cited by 40 publications

References 16 publications

Forensic application of VEGF expression to skin wound age determination

Forensic application of VEGF expression to skin wound age determination

Collagenase Increases the Transcapillary Pressure Gradient and Improves the Uptake and Distribution of Monoclonal Antibodies in Human Osteosarcoma Xenografts

Detection of fibrocytes in human skin wounds and its application for wound age determination

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