Tumor-promoting phorbol esters stimulate C3b and C3b' receptor-mediated phagocytosis in cultured human monocytes.

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  • Author(s): Wright SD; Silverstein SC
  • Source:
    The Journal of experimental medicine [J Exp Med] 1982 Oct 01; Vol. 156 (4), pp. 1149-64.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Rockefeller University Press Country of Publication: United States NLM ID: 2985109R Publication Model: Print Cited Medium: Print ISSN: 0022-1007 (Print) Linking ISSN: 00221007 NLM ISO Abbreviation: J Exp Med Subsets: MEDLINE
    • Publication Information:
      Original Publication: New York, NY : Rockefeller University Press
    • Subject Terms:
    • Abstract:
      Monocytes were isolated in high yield (approximately 80%) and purity (greater than 90%) by Percoll gradient centrifugation and incubated in Teflon culture vessels. Using this culture method, we routinely recovered 80% of the cells originally placed into culture. Studies of the C3b and C3b' receptors of these monocytes showed that the function of both receptors could be dramatically altered by treating the cells with tumor-promoting phorbol esters. Both C3b and C3b' receptors of human monocytes efficiently mediate attachment of erythrocytes coated with the corresponding ligands, but do not promote their ingestion. However, monocytes treated with phorbol myristate acetate (PMA) or phorbol didecanoate ingest C3b- and C3b'-coated erythrocytes. Phorbol esters that are inactive as tumor promoters do not stimulate C3 receptor-mediated phagocytosis. The ability of monocytes to respond to PMA by activation of C3 receptors is developmentally regulated. Freshly isolated monocytes do not take up C3b- or C3b'-coated erythrocytes in response to PMA, but after 3 d of culture they show strong PMA-stimulated uptake. The stimulatory effect of PMA on monocyte C3b and C3b' receptor function occurs within minutes, is stable for hours, is cycloheximide insensitive, and can be inhibited with colchicine. Several lines of evidence indicates that phagocytosis of C3b or C3b'-coated erythrocytes is specifically mediated by the monocytes' C3b and C3b' receptors. First, erythrocytes attached to monocytes with concanavalin A are not ingested when the monocytes are treated with PMA. Second, monocytes plated on IgG-bearing substrates lose Fc receptor activity on their nonadherent surfaces but retain the capacity to ingest C3b- or C3b'-coated erythrocytes after PMA treatment. Third, PMA-treated monocytes plated on C3b-coated surfaces lose C3b receptor activity on their nonadherent surfaces but retain the capacity to ingest C3b'-coated erythrocytes. Conversely, PMA-treated monocytes plated on C3b'-coated surfaces show reduced C3b' receptors activity on their nonadherent surfaces but retain the capacity to ingest C3b-coated erythrocytes.
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    • Grant Information:
      AI 08697 United States AI NIAID NIH HHS; CA 30198 United States CA NCI NIH HHS
    • Accession Number:
      0 (Cations)
      0 (Phorbol Esters)
      0 (Phorbols)
      0 (Receptors, Complement)
      80295-43-8 (Complement C3b)
      98600C0908 (Cycloheximide)
      L36H50F353 (Podophyllotoxin)
      NI40JAQ945 (Tetradecanoylphorbol Acetate)
      SML2Y3J35T (Colchicine)
    • Publication Date:
      Date Created: 19821001 Date Completed: 19830311 Latest Revision: 20190508
    • Publication Date:
      20221213
    • Accession Number:
      PMC2186805
    • Accession Number:
      10.1084/jem.156.4.1149
    • Accession Number:
      7153708