Eur J Pediatr Surg 2021; 31(01): 086-094
DOI: 10.1055/s-0040-1717088
Original Article

Phenotypic Switch of Human Peritoneal Macrophages during Childhood

Nagoud Schukfeh
1   Department of Pediatric Surgery, Hannover Medical School, Hannover, Germany
,
Amr Elyas
1   Department of Pediatric Surgery, Hannover Medical School, Hannover, Germany
,
Dorothee Viemann
2   Department of Pediatric Pulmonology, Hannover Medical School, Hannover, Germany
,
Benno M. Ure
1   Department of Pediatric Surgery, Hannover Medical School, Hannover, Germany
,
Stephanie Froemmel
1   Department of Pediatric Surgery, Hannover Medical School, Hannover, Germany
,
Joon-Keun Park
1   Department of Pediatric Surgery, Hannover Medical School, Hannover, Germany
,
Joachim F. Kuebler
1   Department of Pediatric Surgery, Hannover Medical School, Hannover, Germany
,
1   Department of Pediatric Surgery, Hannover Medical School, Hannover, Germany
› Institutsangaben

Abstract

Introduction Human peritoneal macrophages are resident in the abdominal cavity where they support the specific microenvironmental regulation. We have previously observed a phenotypic switch of murine macrophages during infancy that was associated with a functional development. To investigate the age related changes in human peritoneal macrophages, we analyzed peritoneal macrophages of children undergoing laparoscopic procedures.

Materials and Methods Immunologically healthy children who received minimally invasive surgery in our department were included in this study. In all cases, the written consent was obtained. At the beginning of laparoscopy, physiologic NaCl-solution was instilled and manually removed through the umbilical trocar to gain macrophages. Lavage cells were processed for flow cytometry analysis. CD14+ myeloid cells were monitored for specific lineage marker expression.

Results A total of 21 donors (age: 7 days–18 years) were included and divided into three groups. In all age groups, 97% of myeloid cells expressed CD11b. 70% of these expressed CD14. Three subsets of CD14 cells were detected on the basis of CD14/CD16 expression (CD14 + CD16dim, CD14 + CD16inter, and CD14 + CD16high). In neonates, >80% belonged to the CD14 + CD16high subset, reducing to 30% in adolescents. In none of the cases, the M2 markers CD23 and CD25 were expressed.

Conclusion This is the first study showing that lineage marker expression of peritoneal macrophages in neonates differs from that in adults. The knowledge about neonatal tissue resident macrophages might help to understand their complex interaction and to use specific macrophage properties for therapeutic approaches.



Publikationsverlauf

Eingereicht: 15. Mai 2020

Angenommen: 16. August 2020

Artikel online veröffentlicht:
19. September 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Gordon S, Plüddemann A. Tissue macrophages: heterogeneity and functions. BMC Biol 2017; 15 (01) 53
  • 2 Orecchioni M, Ghosheh Y, Pramod AB, Ley K. Macrophage polarization: different gene signatures in M1(LPS+) vs. classically and M2(LPS-) vs. alternatively activated macrophages. Front Immunol 2019; 10: 1084
  • 3 Wynn TA, Chawla A, Pollard JW. Macrophage biology in development, homeostasis and disease. Nature 2013; 496 (7446): 445-455
  • 4 Röszer T. Understanding the biology of self-renewing macrophages. Cells 2018; 7 (08) 103
  • 5 Lavine KJ, Epelman S, Uchida K. et al. Distinct macrophage lineages contribute to disparate patterns of cardiac recovery and remodeling in the neonatal and adult heart. Proc Natl Acad Sci U S A 2014; 111 (45) 16029-16034
  • 6 Caputa G, Castoldi A, Pearce EJ. Metabolic adaptations of tissue-resident immune cells. Nat Immunol 2019; 20 (07) 793-801
  • 7 Italiani P, Boraschi D. New insights into tissue macrophages: from their origin to the development of memory. Immune Netw 2015; 15 (04) 167-176
  • 8 Martinez FO, Gordon S. The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep 2014; 6 (March): 13
  • 9 Xue J, Schmidt SV, Sander J. et al. Transcriptome-based network analysis reveals a spectrum model of human macrophage activation. Immunity 2014; 40 (02) 274-288
  • 10 Varol C, Mildner A, Jung S. Macrophages: development and tissue specialization. Annu Rev Immunol 2015; 33: 643-675
  • 11 Schmidt SV, Krebs W, Ulas T. et al. The transcriptional regulator network of human inflamma- tory macrophages is defined by open chromatin. Cell Res 2016; 26 (02) 151-170
  • 12 Winterberg T, Vieten G, Feldmann L. et al. Neonatal murine macrophages show enhanced chemotactic capacity upon toll-like receptor stimulation. Pediatr Surg Int 2014; 30 (02) 159-164
  • 13 Bain CC, Jenkins SJ. The biology of serous cavity macrophages. Cell Immunol 2018; 330: 126-135
  • 14 Mao R, Wang C, Zhang F. et al. Peritoneal M2 macrophage transplantation as a potential cell therapy for enhancing renal repair in acute kidney injury. J Cell Mol Med 2019; 2020: 1-14
  • 15 Warren HS, Tompkins RG, Moldawer LL. et al. Mice are not men. Proc Natl Acad Sci U S A 2015; 112 (04) E345
  • 16 Seok J, Warren HS, Cuenca AG. Inflammation and Host Response to Injury, Large Scale Collaborative Research Program. et al. Genomic responses in mouse models poorly mimic human inflammatory diseases. Proc Natl Acad Sci U S A 2013; 110 (09) 3507-3512
  • 17 Schroder K, Irvine KM, Taylor MS. et al. Conservation and divergence in Toll-like receptor 4-regulated gene expression in primary human versus mouse macrophages. Proc Natl Acad Sci U S A 2012; 109 (16) E944-E953
  • 18 Vijayan V, Pradhan P, Braud L. et al. Human and murine macrophages exhibit differential metabolic responses to lipopolysaccharide - a divergent role for glycolysis. Redox Biol 2019; 22 (February): 101147
  • 19 Kelly A, Gunaltay S, McEntee CP. et al. Human monocytes and macrophages regulate immune tolerance via integrin αvβ8-mediated TGFβ activation. J Exp Med 2018; 215 (11) 2725-2736
  • 20 Sattler S, Rosenthal N. The neonate versus adult mammalian immune system in cardiac repair and regeneration. Biochim Biophys Acta 2016; 1863 (7 Pt B): 1813-1821
  • 21 Cassado AdosA, D'Império Lima MR, Bortoluci KR. Revisiting mouse peritoneal macrophages: heterogeneity, development, and function. Front Immunol 2015; 6: 225
  • 22 Winterberg T, Vieten G, Meier T. et al. Distinct phenotypic features of neonatal murine macrophages. Eur J Immunol 2015; 45 (01) 214-224
  • 23 Humphries JE, Corr B, Alexander HD. et al. Why discard the peritoneal macrophages of patients on CAPD?. Br J Haematol 1999; 105 (01) 319-320
  • 24 Bellón T, Martínez V, Lucendo B. et al. Alternative activation of macrophages in human peritoneum: implications for peritoneal fibrosis. Nephrol Dial Transplant 2011; 26 (09) 2995-3005
  • 25 Liao CT, Andrews R, Wallace LE. et al. Peritoneal macrophage heterogeneity is associated with different peritoneal dialysis outcomes. Kidney Int 2017; 91 (05) 1088-1103
  • 26 Cao Q, Wang Y, Wang C. et al. Therapeutic potential of regulatory macrophages generated from peritoneal dialysate in adriamycin nephropathy. Am J Physiol Renal Physiol 2018; 314 (04) F561-F571
  • 27 Hashimoto K, Honda K, Matsui H, Nagashima Y, Oda H. Flow cytometric analysis of ovarian cancer ascites: response of mesothelial cells and macrophages to cancer. Anticancer Res 2016; 36 (07) 3579-3584
  • 28 Ruiz-Alcaraz AJ, Martínez-Banaclocha H, Marín-Sánchez P. et al. Isolation of functional mature peritoneal macrophages from healthy humans. Immunol Cell Biol 2020; 98 (02) 114-126
  • 29 Ruiz-Alcaraz AJ, Carmona-Martínez V, Tristán-Manzano M. et al. Characterization of human peritoneal monocyte/macrophage subsets in homeostasis: Phenotype, GATA6, phagocytic/oxidative activities and cytokines expression. Sci Rep 2018; 8 (01) 12794
  • 30 Shimotakahara A, Kuebler JF, Vieten G, Metzelder ML, Petersen C, Ure BM. Pleural macrophages are the dominant cell population in the thoracic cavity with an inflammatory cytokine profile similar to peritoneal macrophages. Pediatr Surg Int 2007; 23 (05) 447-451
  • 31 Rundgren IM, Bruserud Ø, Ryningen A, Ersvær E. Standardization of sampling and sample preparation for analysis of human monocyte subsets in peripheral blood. J Immunol Methods 2018; 461: 53-62
  • 32 Ruiz-Alcaraz AJ, Tapia-Abellán A, Fernández-Fernández MD. et al. A novel CD14(high) CD16(high) subset of peritoneal macrophages from cirrhotic patients is associated to an increased response to LPS. Mol Immunol 2016; 72: 28-36
  • 33 Lasitschka F, Giese T, Paparella M. et al. Human monocytes downregulate innate response receptors following exposure to the microbial metabolite n-butyrate. Immun Inflamm Dis 2017; 5 (04) 480-492
  • 34 Chen T, Cao Q, Wang Y, Harris DCH. M2 macrophages in kidney disease: biology, therapies, and perspectives. Kidney Int 2019; 95 (04) 760-773