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Erschienen in: International Urogynecology Journal 9/2020

27.02.2020 | Original Article

Age-associated differences in macrophage response in a vaginal wound healing rat model

verfasst von: Ofra Ben Menachem-Zidon, Ilana Parkes, Henry H. Chill, Benjamin Reubinoff, Kathryn Sandberg, Hong Ji, David Shveiky

Erschienen in: International Urogynecology Journal | Ausgabe 9/2020

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Abstract

Introduction and hypothesis

Surgical treatment of pelvic organ prolapse often includes the use of patients’ vaginal connective tissue. Wound healing appears to play an important part in the success of such procedures. The aim of this study was to describe the effect of age on inflammatory processes, specifically macrophage response, involved in vaginal wound healing.

Methods

Twenty-five young (12 weeks old) and 25 old (12 months old) virgin female Fischer rats underwent a standardized 9-mm posterior midline vaginal incision. Tissue samples were taken for histological analysis on days 1, 3, 7, 14 and 30 post-injury. Parameters evaluated included wound area, macrophage number and expression of inflammatory markers including tumor necrosis factor alpha (TNFa), inducible nitric oxide synthase (iNOS), CCR7/CD197, arginase I and CD163/M130.

Results

Microscopic examination of the vaginal wounds over time demonstrated a clear difference between young and old rats in spontaneous healing capacity. The average wound area in young rats 1 day after injury was significantly smaller than in old rats (16.5 ± 1.7 vs. 23.8 ± 1.5 mm2, P < 0.05). At 3 days post-injury, wounds were closed in young rats but still open in old rats (wound area: 13.5 ± 1.5 mm2). Old rats demonstrated a more excessive and sustained macrophage response compared with young rats. They also demonstrated a disordered pattern of macrophage expression over time, with a prolonged expression of TNFa and iNOS in the tissue and a disordered M2 macrophage response.

Conclusion

Excessive and prolonged macrophage response in older rats may contribute to poor wound healing in the vagina.
Literatur
1.
Zurück zum Zitat Freeman RM. Do we really know the outcomes of prolapse surgery? Maturitas. 2010;65:11–4.CrossRef Freeman RM. Do we really know the outcomes of prolapse surgery? Maturitas. 2010;65:11–4.CrossRef
2.
Zurück zum Zitat Deng T, Liao B, Luo D, Shen H, Wang K. Risk factors for mesh erosion after female pelvic floor reconstructive surgery: a systematic review and meta-analysis. BJU Int. 2016;117(2):323–43.CrossRef Deng T, Liao B, Luo D, Shen H, Wang K. Risk factors for mesh erosion after female pelvic floor reconstructive surgery: a systematic review and meta-analysis. BJU Int. 2016;117(2):323–43.CrossRef
3.
Zurück zum Zitat Rajshekhar S, Mukhopadhyay S, Klinge U. Mesh for prolapse surgery: why the fuss? Post Reprod Health. 2015;21(2):69–74.CrossRef Rajshekhar S, Mukhopadhyay S, Klinge U. Mesh for prolapse surgery: why the fuss? Post Reprod Health. 2015;21(2):69–74.CrossRef
4.
Zurück zum Zitat DeLancey JO, Morgan DM, Fenner DE, et al. Comparison of levator ani muscle defects and function in women with and without pelvic organ prolapse. Obstet Gynecol. 2007;109:295–302.CrossRef DeLancey JO, Morgan DM, Fenner DE, et al. Comparison of levator ani muscle defects and function in women with and without pelvic organ prolapse. Obstet Gynecol. 2007;109:295–302.CrossRef
5.
Zurück zum Zitat Chow D, Rodríguez LV. Epidemiology and prevalence of pelvic organ prolapse. Curr Opin Urol. 2013;23(4):293–8.CrossRef Chow D, Rodríguez LV. Epidemiology and prevalence of pelvic organ prolapse. Curr Opin Urol. 2013;23(4):293–8.CrossRef
6.
Zurück zum Zitat Mannella P, Palla G, Bellini M, Simoncini T. The female pelvic floor through midlife and aging. Maturitas. 2013;76:230–4.CrossRef Mannella P, Palla G, Bellini M, Simoncini T. The female pelvic floor through midlife and aging. Maturitas. 2013;76:230–4.CrossRef
7.
Zurück zum Zitat Rortveit G, Hunskaar S. Urinary incontinence and age at the first and last delivery: the Norwegian HUNT/EPINCONT study. Am J Obstet Gynecol. 2006;195:433–8.CrossRef Rortveit G, Hunskaar S. Urinary incontinence and age at the first and last delivery: the Norwegian HUNT/EPINCONT study. Am J Obstet Gynecol. 2006;195:433–8.CrossRef
8.
Zurück zum Zitat Dang C, Ting K, Soo C, Longaker MT, Lorenz HP. Foetal wound healing. Curr Perspect Clin Plast Surg. 2003;30:13–33.CrossRef Dang C, Ting K, Soo C, Longaker MT, Lorenz HP. Foetal wound healing. Curr Perspect Clin Plast Surg. 2003;30:13–33.CrossRef
9.
Zurück zum Zitat Guo S, DiPietro LA. Factors affecting wound healing. J Dent Res. 2010;89:219–29.CrossRef Guo S, DiPietro LA. Factors affecting wound healing. J Dent Res. 2010;89:219–29.CrossRef
10.
Zurück zum Zitat Boon L, Manicourt D, Marbaix E, Vandenabeele M, Vanwijck R. A comparative analysis of healing of surgical cleft lip corrected in utero and in neonates. Plast Reconstr Surg. 1992;89:11–7.CrossRef Boon L, Manicourt D, Marbaix E, Vandenabeele M, Vanwijck R. A comparative analysis of healing of surgical cleft lip corrected in utero and in neonates. Plast Reconstr Surg. 1992;89:11–7.CrossRef
11.
Zurück zum Zitat Shveiky D, Iglesia CB, Onozato ML, Das S, Ji H, Sandberg K. Age has detrimental effects on vaginal wound healing in the rat. Gender Medicine. 2010;7(5):506. Shveiky D, Iglesia CB, Onozato ML, Das S, Ji H, Sandberg K. Age has detrimental effects on vaginal wound healing in the rat. Gender Medicine. 2010;7(5):506.
12.
Zurück zum Zitat Shveiky D, Iglesia CB, Das SS, Ben-Menachem-Zidon O, Chill HH, Ji H, Sandberg K. Age-associated impairments in tissue strength and immune response in a rat vaginal injury model. Int Urogynecol J. 2019. Shveiky D, Iglesia CB, Das SS, Ben-Menachem-Zidon O, Chill HH, Ji H, Sandberg K. Age-associated impairments in tissue strength and immune response in a rat vaginal injury model. Int Urogynecol J. 2019.
13.
Zurück zum Zitat Murray PJ. Macrophage polarization. Annu Rev Physiol. 2017;79:541–66.CrossRef Murray PJ. Macrophage polarization. Annu Rev Physiol. 2017;79:541–66.CrossRef
14.
Zurück zum Zitat Tarique AA, Logan J, Thomas E, Holt PG, Sly PD, Fantino E. Phenotypic, functional, and plasticity features of classical and alternatively activated human macrophages. Am J Respir Cell Mol Biol. 2015;53:676–88.CrossRef Tarique AA, Logan J, Thomas E, Holt PG, Sly PD, Fantino E. Phenotypic, functional, and plasticity features of classical and alternatively activated human macrophages. Am J Respir Cell Mol Biol. 2015;53:676–88.CrossRef
15.
Zurück zum Zitat Hai-xia J, Yu-lian Z, Jing-jing D, et al. The synthetic melanocortin (CKPV)2 exerts anti-fungal, and anti-inflammatory effects against Candida albicans vaginitis via inducing macrophage M2 polarization. PLoS One. 2013;8:1–11. Hai-xia J, Yu-lian Z, Jing-jing D, et al. The synthetic melanocortin (CKPV)2 exerts anti-fungal, and anti-inflammatory effects against Candida albicans vaginitis via inducing macrophage M2 polarization. PLoS One. 2013;8:1–11.
16.
Zurück zum Zitat Ferrante CJ, Leibovitch SJ. Regulation of macrophage polarization and wound healing. Adv Wound Care (New Rochelle). 2012;1(1):10–6.CrossRef Ferrante CJ, Leibovitch SJ. Regulation of macrophage polarization and wound healing. Adv Wound Care (New Rochelle). 2012;1(1):10–6.CrossRef
17.
Zurück zum Zitat Mahbub S, Deburghgraeve CR, Kovacs EJ. Advanced age impairs macrophage polarization. J Interf Cytokine Res. 2012;32(1):18–26.CrossRef Mahbub S, Deburghgraeve CR, Kovacs EJ. Advanced age impairs macrophage polarization. J Interf Cytokine Res. 2012;32(1):18–26.CrossRef
18.
Zurück zum Zitat Campbell L, Saville CR, Murray PJ, Cruickshank SM, Hardman MJ. Local arginase 1 activity is required for cutaneous wound healing. J Invest Derm. 2013;133(10):2461–70.CrossRef Campbell L, Saville CR, Murray PJ, Cruickshank SM, Hardman MJ. Local arginase 1 activity is required for cutaneous wound healing. J Invest Derm. 2013;133(10):2461–70.CrossRef
19.
Zurück zum Zitat Stranks AJ, Hansen AL, Panse I, et al. Autophagy controls acquisition of aging features in macrophages. J Innate Immun. 2015;7:375–91.CrossRef Stranks AJ, Hansen AL, Panse I, et al. Autophagy controls acquisition of aging features in macrophages. J Innate Immun. 2015;7:375–91.CrossRef
20.
Zurück zum Zitat Oishi Y, Manabe I. Macrophages in age-related chronic inflammatory diseases. NPJ Aging Mech Dis. 2016;2:16018.CrossRef Oishi Y, Manabe I. Macrophages in age-related chronic inflammatory diseases. NPJ Aging Mech Dis. 2016;2:16018.CrossRef
21.
Zurück zum Zitat Linehan E, Fitzgerald DC. Ageing and the immune system: focus on macrophages. Eur J Microbiol Immun. 2015;5(1):14–24.CrossRef Linehan E, Fitzgerald DC. Ageing and the immune system: focus on macrophages. Eur J Microbiol Immun. 2015;5(1):14–24.CrossRef
22.
Zurück zum Zitat MacLeod AS, Mansbridge JN. The innate immune system in acute and chronic wounds. Adv Wound Care (New Rochelle). 2016;5(2):65–78.CrossRef MacLeod AS, Mansbridge JN. The innate immune system in acute and chronic wounds. Adv Wound Care (New Rochelle). 2016;5(2):65–78.CrossRef
23.
Zurück zum Zitat Ashcroft GS, Mills SG. Androgen receptor-mediated inhibition of cutaneous wound healing. J Clin Invest. 2002;110(5):615–24.CrossRef Ashcroft GS, Mills SG. Androgen receptor-mediated inhibition of cutaneous wound healing. J Clin Invest. 2002;110(5):615–24.CrossRef
24.
Zurück zum Zitat Ashcroft GS, Jeong MJ, Ashworth JJ, et al. Tumor necrosis factor-alpha (TNFa) is a therapeutic target for impaired cutaneous wound healing. Wound Repair Regen. 2012;20(1):38–49.CrossRef Ashcroft GS, Jeong MJ, Ashworth JJ, et al. Tumor necrosis factor-alpha (TNFa) is a therapeutic target for impaired cutaneous wound healing. Wound Repair Regen. 2012;20(1):38–49.CrossRef
25.
Zurück zum Zitat Huang SM, Wu CS, Chiu MH, et al. High glucose environment induces M1 macrophage polarization that impairs keratinocyte migration via TNFa: an important mechanism to delay the diabetic wound healing. J Dermatol Sci. 2019;96(3):159–67.CrossRef Huang SM, Wu CS, Chiu MH, et al. High glucose environment induces M1 macrophage polarization that impairs keratinocyte migration via TNFa: an important mechanism to delay the diabetic wound healing. J Dermatol Sci. 2019;96(3):159–67.CrossRef
26.
Zurück zum Zitat Leonardi CL, Powers JL, Matheson RT, et al. Etanercept as monotherapy in patients with psoriasis. N Engl J Med. 2003;349(21):2014–22.CrossRef Leonardi CL, Powers JL, Matheson RT, et al. Etanercept as monotherapy in patients with psoriasis. N Engl J Med. 2003;349(21):2014–22.CrossRef
27.
Zurück zum Zitat Menegatti S, Bianchi E, Rogge L. Anti-TNF therapy in spondyloarthritis and related diseases, impact on the immune system and prediction of treatment responses. Front Immunol. 2019;10:382.CrossRef Menegatti S, Bianchi E, Rogge L. Anti-TNF therapy in spondyloarthritis and related diseases, impact on the immune system and prediction of treatment responses. Front Immunol. 2019;10:382.CrossRef
28.
Zurück zum Zitat Adegbola SO, Sahnan K, Warusavitarne J, Hart A, Tozer P. Anti-TNF therapy in Crohn's disease. Int J Mol Sci. 2018;19(8) Adegbola SO, Sahnan K, Warusavitarne J, Hart A, Tozer P. Anti-TNF therapy in Crohn's disease. Int J Mol Sci. 2018;19(8)
Metadaten
Titel
Age-associated differences in macrophage response in a vaginal wound healing rat model
verfasst von
Ofra Ben Menachem-Zidon
Ilana Parkes
Henry H. Chill
Benjamin Reubinoff
Kathryn Sandberg
Hong Ji
David Shveiky
Publikationsdatum
27.02.2020
Verlag
Springer International Publishing
Erschienen in
International Urogynecology Journal / Ausgabe 9/2020
Print ISSN: 0937-3462
Elektronische ISSN: 1433-3023
DOI
https://doi.org/10.1007/s00192-020-04266-9

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