Abstract
Human neutrophils contain receptors for phorbol myristate acetate (PMA), a complex lipid that induces them to generate superoxide (O (2)). Binding of PMA to these receptors displays specificity, reversibility, and high affinity. The receptor's apparent KD was approximately 0.29 nM and multiple copies (approximately 2.1 +/- 0.6 x 10(5)) were present per neutrophil. We found that the timing and magnitude of the neutrophil's respiratory burst were set independently. The onset of O (2) production occurred after a lag that was inversely proportional to the initial concentration of added PMA. The extent (rate) of O (2) production was directly proportional to the fractional occupancy of the receptor by PMA. Dual regulatory controls, such as those we noted when neutrophils were stimulated by PMA, could afford metabolic stability in the face of transient or low intensity stimuli without compromising quick and powerful responses to larger disturbances.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Cohen H. J., Chovaniec M. E. Superoxide generation by digitonin-stimulated guinea pig granulocytes. A basis for a continuous assay for monitoring superoxide production and for the study of the activation of the generating system. J Clin Invest. 1978 Apr;61(4):1081–1087. doi: 10.1172/JCI109007. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DeChatelet L. R., Shirley P. S., Johnston R. B., Jr Effect of phorbol myristate acetate on the oxidative metabolism of human polymorphonuclear leukocytes. Blood. 1976 Apr;47(4):545–554. [PubMed] [Google Scholar]
- Driedger P. E., Blumberg P. M. Specific binding of phorbol ester tumor promoters. Proc Natl Acad Sci U S A. 1980 Jan;77(1):567–571. doi: 10.1073/pnas.77.1.567. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hecker E., Schmidt R. Phorbolesters--the irritants and cocarcinogens of Croton Tiglium L. Fortschr Chem Org Naturst. 1974;31(0):377–467. doi: 10.1007/978-3-7091-7094-6_7. [DOI] [PubMed] [Google Scholar]
- Huberman E., Callaham M. F. Induction of terminal differentiation in human promyelocytic leukemia cells by tumor-promoting agents. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1293–1297. doi: 10.1073/pnas.76.3.1293. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Koeffler H. P., Bar-Eli M., Territo M. Phorbol diester-induced macrophage differentiation of leukemic blasts from patients with human myelogenous leukemia. J Clin Invest. 1980 Nov;66(5):1101–1108. doi: 10.1172/JCI109939. [DOI] [PMC free article] [PubMed] [Google Scholar]
- MARGOLIASH E., FROHWIRT N. Spectrum of horse-heart cytochrome c. Biochem J. 1959 Mar;71(3):570–572. doi: 10.1042/bj0710570. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nakayasu M., Shoji M., Aoki N., Sato S., Miwa M., Sugimura T. Enhancing effect of phorbol esters on induction of differentiation of mouse myeloid leukemia cells by human urinary protein and lipopolysaccharide. Cancer Res. 1979 Nov;39(11):4668–4672. [PubMed] [Google Scholar]
- Newburger P. E., Chovaniec M. E., Cohen H. J. Activity and activation of the granulocyte superoxide-generating system. Blood. 1980 Jan;55(1):85–92. [PubMed] [Google Scholar]
- Repine J. E., White J. G., Clawson C. C., Holmes B. M. Effects of phorbol myristate acetate on the metabolism and ultrastructure of neutrophils in chronic granulomatous disease. J Clin Invest. 1974 Jul;54(1):83–90. doi: 10.1172/JCI107752. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rovera G., O'Brien T. G., Diamond L. Induction of differentiation in human promyelocytic leukemia cells by tumor promoters. Science. 1979 May 25;204(4395):868–870. doi: 10.1126/science.286421. [DOI] [PubMed] [Google Scholar]
- Rovera G., Santoli D., Damsky C. Human promyelocytic leukemia cells in culture differentiate into macrophage-like cells when treated with a phorbol diester. Proc Natl Acad Sci U S A. 1979 Jun;76(6):2779–2783. doi: 10.1073/pnas.76.6.2779. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shoyab M., Todaro G. J. Specific high affinity cell membrane receptors for biologically active phorbol and ingenol esters. Nature. 1980 Dec 4;288(5790):451–455. doi: 10.1038/288451a0. [DOI] [PubMed] [Google Scholar]
- Suzuki Y., Lehrer R. I. NAD(P)H oxidase activity in human neutrophils stimulated by phorbol myristate acetate. J Clin Invest. 1980 Dec;66(6):1409–1418. doi: 10.1172/JCI109994. [DOI] [PMC free article] [PubMed] [Google Scholar]