The megapinosome is an endocytic cell organel that we observed in human macrophages with electron microscopy. In a previous work we showed that it is formed by an endocytic event that we called megapinocytosis. The megapinosome is filled with a membrane surrounded trabecular meshwork that is topologically part of the cytosol. In this work we used scanning transmission electron tomography on high pressure frozen and freeze substituted human macrophages in order to unravel the three-dimensional structure of both the megapinosome and the adjacent structures. The megapinosome consists of the trabecular meshwork and the lacunae which are connected with and topologically equivalent to the cytosol. The surrounding lumen is topologically equivalent to the structures of the vesicular pathway. In addition, we show the connections of the trabecular meshwork with the cytosol and the connection of the megapinosomes to a complex tubular and cisternal system covering a large part of the macrophages that we named megapinosome complex. We assume that our methodological approach, based on high pressure freezing from a defined physiological state and three-dimensional imaging, renders the tubular components of the macrophages better visible than the classical two-dimensional imaging of chemically fixed cells used as a "blueprint" for textbook illustrations. The cell biological functions of the megapinosome are largely enigmatic. Probably, megapinosomes assures storage of surface membranes that can be promptly made available when a macrophage needs to change shape to move through a tissue, to uptake extracellular material or dead cells as well as to fight against microbes.
Keywords: Electron microscopy; Endocytosis; High pressure freezing; Macrophages; Megapinocytosis; STEM tomography.
Copyright © 2020 Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Megapinocytosis: a novel endocytic pathway.Histochem Cell Biol. 2016 Jun;145(6):617-27. doi: 10.1007/s00418-015-1395-2. Epub 2016 Jan 6. Histochem Cell Biol. 2016. PMID: 26733077
Electron microscopy of the red pulp of the dog spleen including vascular arrangements, periarterial macrophage sheaths (ellipsoids), and the contractile, innervated reticular meshwork.Am J Anat. 1981 Jun;161(2):189-218. doi: 10.1002/aja.1001610205. Am J Anat. 1981. PMID: 7258115
Scanning electron microscopy of the trabecular meshwork: understanding the pathogenesis of primary angle closure glaucoma.Indian J Ophthalmol. 2012 May-Jun;60(3):183-8. doi: 10.4103/0301-4738.95868. Indian J Ophthalmol. 2012. PMID: 22569378 Free PMC article.
[Pathological study on the deep scleral flap and external trabecular membrane obtained from non-penetrating trabecular surgery].Zhonghua Yan Ke Za Zhi. 2003 Aug;39(8):462-5. Zhonghua Yan Ke Za Zhi. 2003. PMID: 14642165 Chinese.
Relationship between ultrastructure and specific functions of macrophages.Comp Immunol Microbiol Infect Dis. 1985;8(2):119-33. doi: 10.1016/0147-9571(85)90039-6. Comp Immunol Microbiol Infect Dis. 1985. PMID: 3910340 Review.