Lysosomal enzyme secretion by macrophages during intracellular storage of particles

Our plain-English summary of Lysosomal enzyme secretion by macrophages during intracellular storage of particles, by R.T. Dean, W. Hylton, A.C. Allison (Biochimica et Biophysica Acta, 1979).

The study

• Authors: R.T. Dean, W. Hylton, A.C. Allison
• Journal: Biochimica et Biophysica Acta
• Published: 1979;584(1):57-65
• Cited by: 51 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Cultured mouse peritoneal macrophages containing previously endocytosed zymosan or small-fibre asbestos (but not latex or sucrose) were shown to release selectively into the medium the lysosomal hydrolase beta-N-acetylglucosaminidase. Thus macrophage lysosomal enzyem secretion was experimentally dissociated from endocytosis (as the residual external particles were washed away from the cells). The cells remained viable, and total activities of both N-acetyl-beta-D-glucosaminidase and of lactate dehydrogenase (a cytosol enzyme) rose with time. The relevance of such secretion by macrophages containing stored materials to chronic inflammatory processes is discussed.

In plain English

This laboratory study used macrophages, a type of immune cell, taken from the abdominal cavity of mice and grown in dishes. It asked whether the cells keep releasing lysosomal enzymes after taking in particles, once the particles left outside the cells have been washed away. The materials tested were chrysotile asbestos (a UICC Rhodesian chrysotile reference sample), a milled short-fibre version of it, zymosan (from yeast) and latex particles, and non-particle stimuli including sucrose. Cells that had taken in zymosan or short-fibre asbestos for as little as 2 hours went on releasing the enzyme hexosaminidase over the next 24 hours with no particles in the medium. The cells stayed alive. With ordinary long-fibre chrysotile, significant amounts of fibre stayed attached to the cell surface after washing, and it was relatively ineffective at inducing release in the 24 hours after the cultures were washed. Stored latex and sucrose did not cause this release. The authors suggested that the release probably comes from particles held inside the cells, though other interpretations remain possible. They concluded it is likely relevant to long-lasting inflammation caused by non-digestible materials such as asbestos. This was an experiment on mouse cells in dishes, not a study of people.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: laboratory experiment on cultured mouse cells (in vitro)
• Who was studied: Peritoneal (abdominal cavity) macrophages collected from normal Swiss mice (T.O. strain) and grown in culture; triplicate cultures in all experiments; Clinical Research Centre, Harrow, U.K.
• Exposure: Chrysotile asbestos (UICC standard reference sample of Rhodesian chrysotile) and a short-fibre asbestos made from it by milling. Chrysotile was given at 50 micrograms per ml; Table II lists the short-fibre chrysotile at 100 micrograms per ml. Other stimuli compared were zymosan, latex, dextran sulphate, zymosan-activated serum and sucrose (20 mM).
• Main results:
  • In cultures given zymosan or short-fibre asbestos for only 2 hours and then washed, hexosaminidase release continued during the following 24 hours without the stimulus present.
  • Normal (long-fibre) chrysotile asbestos given for up to 24 hours was relatively ineffective at inducing release in the 24 hours after washing. According to the authors, it did induce release during the first 24 hours (data not shown).
  • After washing, significant amounts of the long fibres of normal chrysotile remained attached to the cell surface. Very few milled short-fibre particles remained attached, and the cells became vacuolated, consistent with the fibres having been taken inside the cells.
  • In experiments varying how long cells were exposed to the particles before a particle-free 24-hour period, release of hexosaminidase, but not of lactate dehydrogenase, was seen. Exposure of 2 to 4 hours gave maximal release.
  • After a 2-hour pulse of short-fibre asbestos, the cells kept up a prolonged selective secretion. Total hexosaminidase activity in the cultures rose considerably between 24 and 96 hours, and lactate dehydrogenase activity also rose. In control cultures, hexosaminidase release reached a maximum of 40% at 96 hours.
  • Macrophages storing zymosan or short-fibre asbestos remained viable and released lysosomal enzymes selectively, across several repeated experiments.
  • Sucrose or latex given for 24 hours did not lead to secretion over the next 24 hours without the material present. Hexosaminidase release was only 2 to 4%.
• The authors' conclusion: The authors concluded that this enzyme release by macrophages storing non-digestible particles is likely relevant to the maintenance of chronic inflammatory reactions caused by materials such as zymosan, asbestos and bacterial components. They wrote that the release probably results directly from the particles being present in the lysosomes, though other interpretations remain possible.
• Limitations the authors state:
  • The authors noted that explanations other than particles acting from inside the lysosomes remain possible.
  • The authors noted that background (basal) enzyme release in control cultures varied, probably depending on the stimulation the macrophages had received in the animal.

Topics

Medical terms in this study, explained in our Lexicon: Macrophage, Lactate Dehydrogenase (LDH).

Related studies

• Spontaneous lysosomal enzyme secretion by a murine macrophage-like cell line — W. Jessup, R.T. Dean (1980)
• Effects of chrysotile on a lysosomal enzyme preparation and on the hydrolytic enzyme activity of cultured alveolar macrophages — R. Desai, R.J. Richards (1983)
• Asbestos induces selective release of lysosomal enzymes from mononuclear phagocytes — P. Davies, A.C. Allison, et al. (1974)
• The selective release of lysosomal acid hydrolases from mouse peritoneal macrophages by stimuli of chronic inflammation — H.U. Schorlemmer, P. Davies, et al. (1977)
• Enhanced lipid peroxidation and lysosomal enzyme activity in the lungs of rats with prolonged pulmonary deposition of crocidolite asbestos — J. Jajte, I. Lao, et al. (1987)
• Inorganic particles induce secretion of a macrophage homologue of platelet-derived growth factor in a density-and time-dependent manner in vitro — R.M. Schapira, A.R. Osornio-Vargas, et al. (1991)

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