Macrophages display varied responses to the tumor promoter, TPA. In this study, a high-affinity receptor for phorbol ester is characterized in a viable alveolar macrophage population. The binding assay is performed using tritiated PDBu and specific binding is demonstrated to be temperature-sensitive. At 37°C, the level of bound ligand reaches maximal binding within 2–5 min but rapidly decays to within 30% of the original specific binding. Equilibrium, however, can be established when the assay is carried out at 4°C. The data indicate that at this temperature maximal binding is reached within 2 h and remains constant there-after. Scatchard analysis shows that the receptor has an apparentK d of 21 nM and each macrophage possesses 2×105 binding sites. Active phorbol derivatives such as TPA and PDBu compete with the labeled ligand for the receptor, whereas the inactive phorbol alcohol does not modulate the specific binding. Mezerein, a related diterpene which has been shown to share some of the properties of phorbol esters, also competes for the binding site. The high-affinity receptor is not affected by zymosan or EIgG phagocytosis. Inflammatory mediators such as prostaglandins E2 and F2a and platelet-activating factor do not compete for the receptor.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Blumberg, P. M. 1980. In vitro studies on the mode of action of the phorbol esters, potent tumor promoters,CRC Crit. Rev. Toxicol. 8:153–197.
Phaire-Washington, L., E. Wang, andS. C. Silverstein. 1980. Phorbol myristate acetate stimulates pinocytosis and membrane spreading in mouse peritoneal macrophages.J. Cell mol. 86:634–640.
Hoidal, J. R., J. E. Repine, G. D. Beall, F. L. Rasp, Jr., andJ. G. White. 1978. The effect of phorbol myristate acetate on the metabolism and ultrastructure of human alveolar macrophages.Am. J. Pathol. 91:469–476.
Laskin, D. L., J. D. Laskin, I. B. Weinstein, andR. A. Carchman. 1980. Modulation of phagocytosis by tumor promoters and epidermal growth factor in normal and transformed macrophages.Cancer Res. 40:1028–1035.
Laskin, D. L., J. D. Laskin, F. K. Kessler, I. B. Weinstein, andR. A. Carchman. 1981. Enhancement of macrophage-induced cytotoxicity by phorbol ester tumor promoters.Cancer Res. 41:4523–4528.
Laskin, D. L., J. D. Laskin, I. B. Weinstein, andR. A. Carchman. 1981. Induction of chemotaxis in mouse peritoneal macrophages by phorbol ester tumor promoters.Cancer Res. 41:1923–1928.
Dahlgren, M. L., P. Davies, andR. J. Bonney. 1980. Phorbol myristate acetate induces the secretion of elastase by populations of resident and elicited mouse peritoneal macrophages.Biochim. Biophys. Acta 630:338–351.
Vassalli, J. D., J. Hamilton, andE. Reich. 1977. Macrophage plasminogen activator: Induction by concanavalin A and phorbol myristate acetate.Cell 11:695–705.
Chang, J., F. M. Wigley, andD. S. Newcombe. 1980. Neutral proteases activation of peritoneal macrophage prostaglandin synthesis.Proc. Natl. Acad. Sci. U.S.A. 77:4736–4740.
Lee, L. S., andI. B. Weinstein. 1978. Uptake of the tumor promoting agent, 12-O-tetradecanoyl-phorbol-13-acetate by HeLa cells.J. Environ. Pathol. Toxicol. 1:627–639.
Schimmel, S. D., G. R. Grotendorst, andR. I. Grove. 1980. Binding of phorbol-12-myristate acetate to cultured myoblasts.Cancer Lett. 9:229–236.
Driedger, P. E., andP. M. Blumberg. 1980. Specific binding of phorbol ester tumor promoters.Proc. Natl. Acad. Sct. U.S.A. 77:567–571.
Dunphy, W. G., K. B. Declos, andP. M. Blumberg. 1980. Characterization of specific binding of [3H]phorbol-12,13-dibutyrate and [3H]phorbol-12-myristate to mouse brain.Cancer Res. 40:3635–3641.
Declos, K. B., D. S. Nagle, andP. M. Blumberg. 1980. Specific binding of phorbol ester tumor promoters to mouse skin.Cell 19:1025–1032.
Shoyab, M., andG. J. Todaro. 1980. Specific high affinity cell membranes receptors for biologically active phorbol and ingenol esters.Nature 288:451–455.
Sando, J. J., M. L. Hilfiker, D. S. Salomon, andJ. J. Farrar. 1981, Specific receptors for phorbol esters in lymphoid cell populations: Role in enhanced production of T-cell growth factor.Proc. Natl. Acad. Sci. U.S.A. 78:1189–1193.
Kielian, M., andZ. A. Cohn. 1981. Phorbol myristate acetate stimulates phagosome-lysosome fusion in mouse macrophages.J. Exp. Med. 154:101–111.
Bonney, R. J., P. D. Wightman, M. E. Dahlgren, P. Davies, F. A. Kuehl, Jr., andJ. L. Humes. 1980. Effect of RNA and protein synthesis inhibitors on the release of inflammatory mediators by macrophages responding to phorbol myristate acetate.Biochim. Biophys. Acta 633:410–421.
Smidt, R., andE. Hecker. 1975. Autoxidation of phorbol esters under normal storage conditions.Cancer Res. 35:1375–1377.
Jones, G. 1973. Release of surface receptors from lymphocytes.J. Immunol. 110:1526–1531.
Brune, K., H. Kalin, R. Schmidt, andE. Hecker, 1978. Inflammatory, tumor promoting activities of polycyclic aromatic hydrocarbons and diterpene esters in mouse skin as compared with their prostaglandin releasing potency in vitro.Cancer Lett. 4:333–342.
About this article
Cite this article
Chang, J. Characterization of a high-affinity receptor for phorbol esters in rat alveolar macrophages. Inflammation 7, 15–23 (1983). https://doi.org/10.1007/BF00918004
- Varied Response
- Inflammatory Mediator
- Specific Binding
- Alveolar Macrophage