Abstract
Purified human PMNs secrete plasminogen activator. This secretion is stimulated by Con A and low concentrations of PMA, and is inhibited by low concentrations of glucocorticoids, and by cAMP, actinomycin D, and cycloheximide. In contrast, the release of granule-bound enzymes, such as elastase, is achieved only at higher concentrations of PMA, and is not affected by any of the inhibitors that block plasminogen activator production. These results show that the production of plasminogen activatory by PMNs is controlled by agents that affect inflammations, and that this control is not shared by other lytic enzymes known to be associated with these cells. This suggests a particular role for plasminogen activator in the response pattern of PMNs and also supports the concept, previously developed for macrophages, that the secretion of this enzyme is correlated with cell migration in vivo.
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- BOGGS D. R., ATHENS J. W., CARTWRIGHT G. E., WINTROBE M. M. THE EFFECT OF ADRENAL GLUCOCORTICOSTEROIDS UPON THE CELLULAR COMPOSITION OF INFLAMMATORY EXUDATES. Am J Pathol. 1964 May;44:763–773. [PMC free article] [PubMed] [Google Scholar]
- Bainton D. F., Farquhar M. G. Differences in enzyme content of azurophil and specific granules of polymorphonuclear leukocytes. I. Histochemical staining of bone marrow smears. J Cell Biol. 1968 Nov;39(2):286–298. doi: 10.1083/jcb.39.2.286. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Berlin R. D. Effect of concanavalin A on phagocytosis. Nat New Biol. 1972 Jan 12;235(54):44–45. doi: 10.1038/newbio235044a0. [DOI] [PubMed] [Google Scholar]
- Bourne H. R., Lehrer R. I., Lichtenstein L. M., Weissmann G., Zurier R. Effects of cholera enterotoxin on adenosine 3',5'-monophosphate and neutrophil function. Comparison with other compounds which stimulate leukocyte adenyl cyclase. J Clin Invest. 1973 Mar;52(3):698–708. doi: 10.1172/JCI107231. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bowers W. E., Finkenstaedt J. T., de Duve C. Lysosomes in lymphoid tissue. I. The measurement of hydrolytic activities in whole homogenates. J Cell Biol. 1967 Feb;32(2):325–337. doi: 10.1083/jcb.32.2.325. [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]
- Dewald B., Rindler-Ludwig R., Bretz U., Baggiolini M. Subcellular localization and heterogeneity of neutral proteases in neutrophilic polymorphonuclear leukocytes. J Exp Med. 1975 Apr 1;141(4):709–723. doi: 10.1084/jem.141.4.709. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Estensen R. D., White J. G., Holmes B. Specific degranulation of human polymorphonuclear leukocytes. Nature. 1974 Mar 22;248(446):347–348. doi: 10.1038/248347a0. [DOI] [PubMed] [Google Scholar]
- GAREN A., LEVINTHAL C. A fine-structure genetic and chemical study of the enzyme alkaline phosphatase of E. coli. I. Purification and characterization of alkaline phosphatase. Biochim Biophys Acta. 1960 Mar 11;38:470–483. doi: 10.1016/0006-3002(60)91282-8. [DOI] [PubMed] [Google Scholar]
- Golde D. W., Bersch N., Quan S. G., Cline M. J. Inhibition of murine granulopoiesis in vitro by dexamethasone. Am J Hematol. 1976;1(4):369–373. doi: 10.1002/ajh.2830010402. [DOI] [PubMed] [Google Scholar]
- Goldstein I. M., Hoffstein S. T., Weissmann G. Mechanisms of lysosomal enzyme release from human polymorphonuclear leukocytes. Effects of phorbol myristate acetate. J Cell Biol. 1975 Sep;66(3):647–652. doi: 10.1083/jcb.66.3.647. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goldstein I. M., Wünschmann B., Astrup T., Henderson E. S. Effects of bacterial endotoxin on the fibrinolytic activity of normal human leukocytes. Blood. 1971 Apr;37(4):447–453. [PubMed] [Google Scholar]
- Gordon S., Todd J., Cohn Z. A. In vitro synthesis and secretion of lysozyme by mononuclear phagocytes. J Exp Med. 1974 May 1;139(5):1228–1248. doi: 10.1084/jem.139.5.1228. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gordon S., Unkeless J. C., Cohn Z. A. Induction of macrophage plasminogen activator by endotoxin stimulation and phagocytosis: evidence for a two-stage process. J Exp Med. 1974 Oct 1;140(4):995–1010. doi: 10.1084/jem.140.4.995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hamilton J., Vassalli J. D., Reich E. Macrophage plasminogen activator: induction by asbestos is blocked by anti-inflammatory steroids. J Exp Med. 1976 Dec 1;144(6):1689–1694. doi: 10.1084/jem.144.6.1689. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hoffstein S., Soberman R., Goldstein I., Weissmann G. Concanavalin A induces microtubule assembly and specific granule discharge in human polymorphonuclear leukocytes. J Cell Biol. 1976 Mar;68(3):781–787. doi: 10.1083/jcb.68.3.781. [DOI] [PMC free article] [PubMed] [Google Scholar]
- KNOBLOCH H., PASAMANICK B. Psychiatry: the epidemiology of mental subnormality. Annu Rev Med. 1962;13:361–370. doi: 10.1146/annurev.me.13.020162.002045. [DOI] [PubMed] [Google Scholar]
- Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
- Moore D. M., Murphy P. A., Chesney P. J., Wood W. B., Jr Synthesis of endogenous pyrogen by rabbit leukocytes. J Exp Med. 1973 May 1;137(5):1263–1274. doi: 10.1084/jem.137.5.1263. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nordlund J. J., Root R. K., Wolff S. M. Studies on the origin of human leukocytic pyrogen. J Exp Med. 1970 Apr 1;131(4):727–743. doi: 10.1084/jem.131.4.727. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ohlsson K., Olsson I. The neutral proteases of human granulocytes. Isolation and partial characterization of granulocyte elastases. Eur J Biochem. 1974 Mar 1;42(2):519–527. doi: 10.1111/j.1432-1033.1974.tb03367.x. [DOI] [PubMed] [Google Scholar]
- Ohlsson K., Olsson I. The neutral proteases of human granulocytes. Isolation and partial characterization of two granulocyte collagenases. Eur J Biochem. 1973 Jul 16;36(2):473–481. doi: 10.1111/j.1432-1033.1973.tb02932.x. [DOI] [PubMed] [Google Scholar]
- Opie E. L. ENZYMES AND ANTI-ENZYMES OF INFLAMMATORY EXUDATES. J Exp Med. 1905 Jun 10;7(3):316–334. doi: 10.1084/jem.7.3.316. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ossowski L., Quigley J. P., Kellerman G. M., Reich E. Fibrinolysis associated with oncogenic transformation. Requirement of plasminogen for correlated changes in cellular morphology, colony formation in agar, and cell migration. J Exp Med. 1973 Nov 1;138(5):1056–1064. doi: 10.1084/jem.138.5.1056. [DOI] [PMC free article] [PubMed] [Google Scholar]
- PARRY R. M., Jr, CHANDAN R. C., SHAHANI K. M. A RAPID AND SENSITIVE ASSAY OF MURAMIDASE. Proc Soc Exp Biol Med. 1965 Jun;119:384–386. doi: 10.3181/00379727-119-30188. [DOI] [PubMed] [Google Scholar]
- Repine J. E., White J. G., Clawson C. C., Holmes B. M. The influence of phorbol myristate acetate on oxygen consumption by polymorphonuclear leukocytes. J Lab Clin Med. 1974 Jun;83(6):911–920. [PubMed] [Google Scholar]
- Rifkin D. B., Crowe R. M. A sensitive assay for elastase employing radioactive elastin coupled to sepharose. Anal Biochem. 1977 May 1;79(1-2):268–275. doi: 10.1016/0003-2697(77)90402-x. [DOI] [PubMed] [Google Scholar]
- Rindler-Ludwig R., Braunsteiner H. Cationic proteins from human neutrophil granulocytes. Evidence for their chymotrypsin-like properties. Biochim Biophys Acta. 1975 Feb 27;379(2):606–617. doi: 10.1016/0005-2795(75)90167-1. [DOI] [PubMed] [Google Scholar]
- Romeo D., Zabucchi G., Rossi F. Reversible metabolic stimulation of polymorphonuclear leukocytes and macrophages by concanavalin A. Nat New Biol. 1973 May 23;243(125):111–112. [PubMed] [Google Scholar]
- Strickland S., Beers W. H. Studies on the role of plasminogen activator in ovulation. In vitro response of granulosa cells to gonadotropins, cyclic nucleotides, and prostaglandins. J Biol Chem. 1976 Sep 25;251(18):5694–5702. [PubMed] [Google Scholar]
- Unkeless J. C., Gordon S., Reich E. Secretion of plasminogen activator by stimulated macrophages. J Exp Med. 1974 Apr 1;139(4):834–850. doi: 10.1084/jem.139.4.834. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vassalli J. D., Hamilton J., Reich E. Macrophage plasminogen activator: induction by concanavalin A and phorbol myristate acetate. Cell. 1977 Jul;11(3):695–705. doi: 10.1016/0092-8674(77)90086-1. [DOI] [PubMed] [Google Scholar]
- Vassalli J. D., Hamilton J., Reich E. Macrophage plasminogen activator: modulation of enzyme production by anti-inflammatory steroids, mitotic inhibitors, and cyclic nucleotides. Cell. 1976 Jun;8(2):271–281. doi: 10.1016/0092-8674(76)90011-8. [DOI] [PubMed] [Google Scholar]
- Vassalli J. D., Reich E. Macrophage plasminogen activator: induction by products of activated lymphoid cells. J Exp Med. 1977 Feb 1;145(2):429–437. doi: 10.1084/jem.145.2.429. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ward P. A. The chemosuppression of chemotaxis. J Exp Med. 1966 Aug 1;124(2):209–226. doi: 10.1084/jem.124.2.209. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wünschmann-Henderson B., Astrup T. Inhibition by hydrocortison of plasminogen activator production in rat tongue organ cultures. Lab Invest. 1974 Apr;30(4):427–433. [PubMed] [Google Scholar]