Cellular and Molecular Life Sciences CMLS

, Volume 59, Issue 8, pp 1358–1365

An immunohistochemical study of the clearance of apoptotic cellular fragments

  • M. P. G. Leers
  • V. Björklund
  • B. Björklund
  • H. Jörnvall
  • M. Nap

DOI: 10.1007/s00018-002-8513-8

Cite this article as:
Leers, M., Björklund, V., Björklund, B. et al. CMLS, Cell. Mol. Life Sci. (2002) 59: 1358. doi:10.1007/s00018-002-8513-8

Abstract.

We investigated the distribution and fate of apoptotic bodies during human development and in the adult, using an antibody (M30) that recognizes a neo-epitope formed early in the apoptotic cascade by caspase cleavage of cytokeratin 18. In the fetus, we found extensive accumulation of M30-positive, non-phagocytosed fragments in the red pulp of the spleen, subcutaneous and submucosal vessels, the interstitium of the lung, and the glomerular mesangium of the kidneys. In the liver, M30-immunoreactive fragments were found inside macrophages in the sinusoids. The number of these fragments and the intensity of the immunostaining increased with the gestational age of the fetus. In the adult, M30-positive fragments were barely detectable in normal tissues. However, many pathological situations, including both chronic degenerative processes and metastatic cancer, were associated with accumulation of M30-positive fragments in the red pulp of the spleen. In the liver and kidney, no fragments could be detected. Remarkably, 13 of the 16 patients with metastasized cancer showed pronounced accumulation of M30-positive fragments containing hematoxylin-reactive material in the red pulp of the spleen. In the non-cancerous cases, such DNA-containing fragments were only seen in 9 of 94 cases. The results show that when apoptotic activity is high, as during development in the fetus or during metastasis and other pathological processes in the adult, the phagocytic clearance of apoptotic bodies can be overloaded. These apoptotic fragments then accumulate in the spleen. The visual detection of apoptotic fragments is concluded to reflect increased cell turnover.

Key words. Apoptosis; immunohistochemistry; caspase-cleaved keratin; human development; macrophage; spleen; liver. 

Copyright information

© Birkhäuser Verlag, 2002

Authors and Affiliations

  • M. P. G. Leers
    • 1
  • V. Björklund
    • 2
  • B. Björklund
    • 2
  • H. Jörnvall
    • 3
  • M. Nap
    • 1
  1. 1.Department of Pathology, Atrium Medical Center Heerlen, PO Box 4446, 6401 CX Heerlen (The Netherlands), Fax +31 45 5766502, e-mail: m.leers@gozl.nl NL
  2. 2.Cancer Council, Stockholm (Sweden)SE
  3. 3.Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77 Stockholm (Sweden)SE

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