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Shedding of CD44 from PMA-differentiated U-937 cells is enhanced by treatment with mineral particles

Our plain-English summary of Shedding of CD44 from PMA-differentiated U-937 cells is enhanced by treatment with mineral particles, by N. Trabelsi, A. Greffard, J.C. Pairon, et al (Biochemical and Biophysical Research Communications, 1998).

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The study

Abstract

In this report, we show that enhanced shedding of CD44 might contribute to the down-regulation of this receptor observed after phagocytosis of MnO2 particles by PMA-differentiated U-937. The apparent Mr of the soluble CD44 detected in culture supernatants was slightly lower than that of the membrane form suggesting that shedding resulted from proteolytic cleavage. Increased shedding of CD44 was also noted with other mineral particles (chrysotile and DQ12) but to a lower extent whereas some (TiO2 and amosite) had no effect on this process. These results indicate that shedding enhancement was particle-specific rather than a general consequence of phagocytosis. The ability of the particles to enhance CD44 shedding was not directly dependent on their cytotoxic potency. Different patterns of reactivity were noted with CD11b, suggesting that the underlying mechanisms are specific.

Copyright 1998 Academic Press.

In plain English

This was a laboratory cell-culture experiment. Human U-937 monocytic cells were differentiated for four days with 0.162 mM PMA, then exposed for 48 hours to mineral particles and fibers at 50 micrograms per square centimetre: titanium dioxide (TiO2), manganese dioxide (MnO2), crystalline silica (DQ12), and UICC Rhodesian chrysotile and amosite. CD44 was measured in cell lysates, and CD44, CD11b and CD14 in concentrated culture supernatants, by Western blotting; viability was measured by the MTT assay. Cellular CD44 fell by nearly 80 percent with MnO2, 30-35 percent with chrysotile or amosite, and by about 4 and 12 percent with DQ12 and TiO2. Soluble CD44 in the medium was roughly 3-fold the untreated control with MnO2 and 1.7-fold with DQ12 or chrysotile, with no significant change for TiO2 or amosite; the soluble form ran slightly smaller than the membrane form. Soluble CD11b rose with DQ12, chrysotile or amosite; no soluble CD14 was detected. Chrysotile was reported as the most cytotoxic particle, decreasing viability by about 60 percent. The authors concluded that increased shedding appeared to contribute to the MnO2-induced loss of CD44.

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: in vitro experimental study on a differentiated human cell line (U-937) treated with mineral particles and fibers for 48 hours
  • Who was studied: Human U-937 monocytic cell line differentiated with PMA for four days; laboratory study, INSERM Unit 139, Creteil, France (published 1998)
  • Exposure: Crystalline silica (quartz DQ12), manganese dioxide, titanium dioxide, and UICC Rhodesian chrysotile and amosite asbestos, each at 50 micrograms per square centimetre of culture surface for 48 hours
  • Main results:
    • Cellular CD44 expression was reduced by nearly 80% in MnO2-treated cells
    • Moderate reductions in cellular CD44 of about 4% and 12% were found with DQ12 and TiO2 respectively
    • Chrysotile or amosite treatment gave a 30-35% decrease in cellular CD44 expression
    • Soluble CD44 in the medium of MnO2-treated cells was roughly 3-fold the amount in the untreated control
    • Soluble CD44 after DQ12 or chrysotile treatment was 1.7-fold that of untreated cells
    • No significant changes in soluble CD44 were seen with TiO2 or amosite
    • The apparent Mr of soluble CD44 in supernatants was slightly lower than membrane CD44, which the authors took to suggest release by proteolytic cleavage
    • Soluble CD11b was markedly increased by treatment with DQ12, chrysotile or amosite, whereas MnO2 had only a moderate effect
    • No soluble CD14 was detected in supernatants of control or particle-treated cells
    • In the MTT viability assay the most cytotoxic particle was chrysotile, which decreased cell viability by about 60%
  • The authors' conclusion: The authors concluded that increased shedding appeared to contribute significantly to the down-regulation of CD44 induced by MnO2, that the effect was particle-specific rather than a general consequence of phagocytosis, and that the different patterns for CD44 and CD11b suggested specific mechanisms
  • Limitations the authors state:
    • The authors stated that the mechanisms of cell surface protein shedding are still unclear
    • The authors presented their proposed mechanism (particle contact with CD44 at the cell surface) as speculation

Topics

Medical terms in this study, explained in our Lexicon: Phagocytosis, Chrysotile, Amosite.

Browse more research in Biochemical and Biophysical Research Communications, or return to medical research.

Cited on this site

How to cite it

Cite the study

N. Trabelsi, A. Greffard, J.C. Pairon, L. Kheuang, J. Bignon, M.C. Jaurand, et al. Shedding of CD44 from PMA-differentiated U-937 cells is enhanced by treatment with mineral particles. Biochemical and Biophysical Research Communications 1998;245(1):240-5. doi:10.1006/bbrc.1998.8405. PMID: 9535816.

Cite our summary

“Shedding of CD44 from PMA-differentiated U-937 cells is enhanced by treatment with mineral particles.” AsbestosClaims.Law Library. https://asbestosclaims.law/library/research/shedding-of-cd44-from-pma-differentiated-u-937-cells-is-enhanced-by.

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