Skip to main content
Log in

Morphological and phenotypical diversity of eosinophils in the rat ileum

  • Regular Article
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

Eosinophils are abundantly present in intestinal mucosa. However, the morphological characteristics of their cellular population are still largely unknown. In this study, we examine their characteristics in the rat ileal mucosa using histological and ultrastructural methods. The results indicated that ileal eosinophils could be distinguished into two main groups based on their nuclear shapes and distribution: eosinophils with spheric or reniform nuclei mainly localized in the villous region and eosinophils with annular or bacilliform nuclei as the major population around crypts. Immunohistochemical analysis revealed that all eosinophils in the lamina propria (LP) were immunopositive for CD11b, whereas eosinophils in LP of the intestinal villus but not those in LP around the crypt, were immunopositive for CD11c. Three-dimensional ultrastructural analysis using serial block-face scanning electron microscopy showed that the eosinophils with spheric or reniform nuclei were abundant in the upper portions of the intestinal villus, whereas those with annular nuclei were abundant in the lower portions of the intestinal villus and around crypts. The eosinophils with spheric or reniform nuclei possessed broader cellular bodies with greater abundance of surface projections compared with those with annular nuclei. Eosinophils in the upper portions of intestinal villus frequently extended their cellular bodies into the intraepithelial space. The number of total and eosinophil-specific granules was positively correlated with the minor axis of the nuclear holes in the annular nuclei. These data suggest that ileal eosinophils exhibit not homogenous but rather diverse characteristics, possible due to the mixture of eosinophils at different maturation and/or activation stages.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Amihai D, Meilijson I, Terkel J, Hammel I (2015) Quantitative microscopy of mole rat eosinophil granule morphology. Cell Tissue Res 362:139–151

    Article  Google Scholar 

  • Anderson DC, Springer TA (1987) Leukocyte adhesion deficiency: an inherited defect in the mac-1, LFA-1, and p150,95 glycoproteins. Annu Rev Med 38:175–194

    Article  CAS  Google Scholar 

  • Bainton DF, Farquhar MG (1970) Segregation and packaging of granule enzymes in eosinophilic leukocytes. J Cell Biol 45:54–73

    Article  CAS  Google Scholar 

  • Balázs A, Rappay G (1967) Differentiation of the myelon and the life cycle of granulocytes in rats. Acta Biol Hung 18:371–386

    Google Scholar 

  • Bernstein CN, Sargent M, Gallatin WM, Wilkins J (1996) β2-integrin/intercellular adhesion molecule (ICAM) expression in the normal human intestine. Clin Exp Immunol 106:160–169

    CAS  PubMed  Google Scholar 

  • Bouffi C, Rochman M, Zust CB, Stucke EM, Kartashov A, Fulkerson PC, Barski A, Rothenberg ME (2013) IL-33 markedly activates murine eosinophils by an NF-κB-dependent mechanism differentially dependent upon an IL-4-driven autoinflammatory loop. J Immunol 191:4317–4325

    Article  CAS  Google Scholar 

  • Carlens J, Wahl B, Ballmaier M, Bulfone-Paus S, Förster R, Pabst O (2009) Common γ-chain-dependent signals confer selective survival of eosinophils in the murine small intestine. J Immunol 183:5600–5607

    Article  CAS  Google Scholar 

  • Christensen JL, Wright DE, Wagers AJ, Weissman IL (2004) Circulation and chemotaxis of fetal hematopoietic stem cells. PLoS Biol 2:368–377

    Article  CAS  Google Scholar 

  • Chu VT, Beller A, Rausch S, Strandmark J, Zänker M, Arbach O, Kruglov A, Berek C (2014) Eosinophils promote generation and maintenance of immunoglobulin-A-expressing plasma cells and contribute to gut immune homeostasis. Immunity 40:582–593

    Article  CAS  Google Scholar 

  • Diamond MS, Staunton DE, De Fougerolles AR, Stacker SA, Garcia-Aguilar J, Hibbs ML, Springer TA (1990) ICAM-1 (CD54): a counter-receptor for mac-1 (CD11b/CD18). J Cell Biol 111:3129–3139

    Article  CAS  Google Scholar 

  • Dias FF, Amaral KB, Malta KK, Silva TP, Rodrigues GSC, Rosa FM, Rodrigues GOL, Costa VV, Chiarini-Garcia H, Weller PF, Melo RCN (2018) Identification of piecemeal degranulation and vesicular transport of MBP-1 in liver-infiltrating mouse eosinophils during acute experimental Schistosoma mansoni infection. Front Immunol 9:3019

    Article  CAS  Google Scholar 

  • Diggs LW, Sturm D, Bell A (1956) The morphology of human blood cells. W. B. Saunders Company 64-68

  • Erdei A, Lukácsi S, Mácsik-Valent B, Nagy-Baló Z, Kurucz I, Bajtay Z (2019) Non-identical twins: different faces of CR3 and CR4 in myeloid and lymphoid cells of mice and men. Semin Cell Dev Biol 85:110–121

    Article  CAS  Google Scholar 

  • Flanders A, Galbraith W, Marshall PN (1984) Microspectrophotometric studies of Romanowsky stained blood cells. IV. Maturation of myeloid and erythroid cell lines in bone marrow. Stain Technol 59:91–103

    Article  CAS  Google Scholar 

  • Fu J, Zuber J, Martinez M, Shonts B, Obradovic A, Wang H, Lau SP, Xia A, Waffarn EE, Frangaj K, Savage TM, Simpson MT, Yang S, Guo XV, Miron M, Senda T, Rogers K, Rahman A, Ho SH, Shen Y, Griesemer A, Farber DL, Kato T, Sykes M (2019) Human intestinal allografts contain functional hematopoietic stem and progenitor cells that are maintained by a circulating pool. Cell Stem Cell 24:227–239

    Article  CAS  Google Scholar 

  • Fulkerson PC, Schollaert KL, Bouffi C, Rothenberg ME (2014) IL-5 triggers a cooperative cytokine network that promotes eosinophil precursor maturation. J Immunol 193:4043–4052

    Article  CAS  Google Scholar 

  • Griffith JW, Sokol CL, Luster AD (2014) Chemokines and chemokine receptors: positioning cells for host defense and immunity. Annu Rev Immunol 32:659–702

    Article  CAS  Google Scholar 

  • Jung Y, Wen T, Mingler MK, Caldwell JM, Wang YH, Chaplin DD, Lee EH, Jang MH, Woo SY, Seoh JY, Miyasaka M, Rothenberg ME (2015) IL-1β in eosinophil-mediated small intestinal homeostasis and IgA production. Mucosal Immunol 8:930–942

    Article  CAS  Google Scholar 

  • Lukácsi S, Nagy-Baló Z, Erdei A, Sándor N, Bajtay Z (2017) The role of CR3 (CD11b/CD18) and CR4 (CD11c/CD18) in complement-mediated phagocytosis and podosome formation by human phagocytes. Immunol Lett 189:64–72

    Article  Google Scholar 

  • Mantani Y, Haruta T, Nishida M, Yokoyama T, Hoshi N, Kitagawa H (2019) Three-dimensional analysis of fibroblast-like cells in the lamina propria of the rat ileum using serial block-face scanning electron microscopy. J Vet Med Sci 81:454–465

    Article  CAS  Google Scholar 

  • Melo RCN, Spencer LA, Perez SAC, Ghiran I, Dvorak AM, Weller PF (2005) Human eosinophils secrete preformed, granule-stored interleukin-4 through distinct vesicular compartments. Traffic 6:1047–1057

    Article  CAS  Google Scholar 

  • Mishra A, Hogan SP, Lee JJ, Foster PS, Rothenberg ME (1999) Fundamental signals that regulate eosinophil homing to the gastrointestinal tract. J Clin Invest 103:1719–1727

    Article  CAS  Google Scholar 

  • Nguyen HB, Thai TQ, Saitoh S, Wu B, Saitoh Y, Shimo S, Fujitani H, Otobe H, Ohno N (2016) Conductive resins improve charging and resolution of acquired images in electron microscopic volume imaging. Sci Rep 6:23721

    Article  CAS  Google Scholar 

  • Parkos CA, Colgan SP, Diamond MS, Nusrat A, Liang TW, Springer TA, Madara JL (1996) Expression and polarization of intercellular adhesion molecule-1 on human intestinal epithelia: consequences for CD11b/CD18-mediated interactions with neutrophils. Mol Med 2:489–505

    Article  CAS  Google Scholar 

  • Rothenberg ME, Hogan SP (2006) The eosinophil. Annu Rev Immunol 24:147–174

    Article  CAS  Google Scholar 

  • Sándor N, Lukácsi S, Ungai-Salánki R, Orgován N, Szabó B, Horváth R, Erdei A, Bajtay Z (2016) CD11c/CD18 dominates adhesion of human monocytes, macrophages and dendritic cells over CD11b/CD18. PLoS One 11:e0163120

    Article  Google Scholar 

  • Smart CJ, Calabrese A, Oakes DJ, Howdle PD, Trejdosiewicz LK (1991) Expression of the LFA-1 β2 integrin (CD11a/CD18) and ICAM-1 (CD54) in normal and coeliac small bowel mucosa. Scand J Immunol 34:299–305

    Article  CAS  Google Scholar 

  • Spencer LA, Bonjour K, Melo RCN, Weller PF (2014) Eosinophil secretion of granule-derived cytokines. Front Immunol 5:496

    Article  Google Scholar 

  • Springer TA, Dustin ML, Kishimoto TK, Marlin SD (1987) The lymphocyte function-associated LFA-1, CD2, and LFA-3 molecules: cell adhesion receptors of the immune system. Annu Rev Immunol 5:223–252

    Article  CAS  Google Scholar 

  • Springer TA (1990) Adhesion receptors of the immune system. Nature 346:425–434

    Article  CAS  Google Scholar 

  • Springer TA (1994) Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 76:301–314

    Article  CAS  Google Scholar 

  • Sugawara R, Lee EJ, Jang MS, Jeun EJ, Hong CP, Kim JH, Park A, Yun CH, Hong SW, Kim YM, Seoh JY, Jung Y, Surh CD, Miyasaka M, Yang BG, Jang MH (2016) Small intestinal eosinophils regulate Th17 cells by producing IL-1 receptor antagonist. J Exp Med 213:555–567

    Article  CAS  Google Scholar 

  • Weller PF, Spencer LA (2017) Functions of tissue-resident eosinophils. Nat Rev Immunol 17:746–760

    Article  CAS  Google Scholar 

  • Willebrand R, Voehringer D (2017) Regulation of eosinophil development and survival. Curr Opin Hematol 24:9–15

    Article  Google Scholar 

  • Xenakis JJ, Howard ED, Smith KM, Olbrich CL, Huang Y, Anketell D, Maldonado S, Cornwell EW, Spencer LA (2018) Resident intestinal eosinophils constitutively express antigen presentation markers and include two phenotypically distinct subsets of eosinophils. Immunology 154:298–308

    Article  CAS  Google Scholar 

  • Yuasa H, Mantani Y, Masuda N, Nishida M, Arai M, Yokoyama T, Tsuruta H, Kawano J, Hoshi N, Kitagawa H (2017) Mechanism of M-cell differentiation accelerated by proliferation of indigenous bacteria in rat Peyer’s patches. J Vet Med Sci 79:1826–1835

    Article  CAS  Google Scholar 

Download references

Acknowledgments

Dr. N. Ohno (Jichi Medical University) kindly provided the Ketjen black to prevent the charging of samples.

Funding

This study was supported by the Japan Society for the Promotion of Science (grant nos. 15K07766 and 16K18813).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Youhei Mantani.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This study was approved by the Institutional Animal Care and Use Committee (permission numbers: 25-06-01 and 30-05-01). All procedures performed in studies involving animals were in accordance with the ethical standards of the institution (the Kobe University Animal Experimentation Regulations) or practice at which the studies were conducted.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Arai, M., Mantani, Y., Nakanishi, S. et al. Morphological and phenotypical diversity of eosinophils in the rat ileum. Cell Tissue Res 381, 439–450 (2020). https://doi.org/10.1007/s00441-020-03209-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-020-03209-6

Keywords

Navigation