Induction of macrophage plasminogen activator by endotoxin stimulation and phagocytosis: evidence for a two-stage process - PubMed (original) (raw)

Induction of macrophage plasminogen activator by endotoxin stimulation and phagocytosis: evidence for a two-stage process

S Gordon et al. J Exp Med. 1974.

Abstract

The injection of thioglycollate medium into the peritoneal cavity of the mouse induces high levels of macrophage fibrinolytic activity due to the production and secretion of a plasminogen activator, a trypsinlike serine protease, which is absent in unstimulated macrophages. Intraperitoneal injection of endotoxin or mineral oil can stimulate only a fraction (<10%) of the fibrinolytic activity of thioglycollate cells, similar to the partial stimulation (<10%) seen 1-2 days after phagocytosis of latex or SRBC by unstimulated macrophages. The endotoxin-stimulated macrophages contain and release relatively low levels of plasminogen activator, but these primed cells can be triggered to produce and secrete high levels of enzyme, by phagocytosis of latex. Under conditions where the plasminogen activator is induced and secreted, there are no effects on the production and/or release of lysozyme or intracellular acid hydrolases, Discovery of a two-stage procedure for inducing macrophage plasminogen activator made it possible to study the role of cell priming and phagocytosis separately. Endotoxin was a more effective priming agent, weight for weight, than lipid A:BSA complex. Secretion of the plasminogen activator was induced only by thioglycollate, or endotoxin and latex. In situ fibrinolysis was induced by these agents and mineral oil, BCG, and fetal calf serum, in decreasing order of effectiveness. Phagocytosis of latex in all cases except thioglycollate stimulation, increased fibrinolytic activity from three- to sixfold. Latex and a variety of other particles such as M. lysodeikticus, aggregated gamma-globulin and immune complexes showed dose-dependent stimulation of fibrinolysis by endotoxin-primed macrophages. Although the initial phagocytic trigger was not specific for the substance employed, the ability to induce a sustained response depended on the persistence of the phagocytized particle within the cell. Fibrinolysis and secretion of plasminogen activator continued at high levels for at least 9 days after uptake of latex, a nondigestible particle, whereas plasminogen activator was secreted only transiently after ingestion of rapidly digested M. lysodeikticus. The induction of plasminogen activator secretion provides a mechanism by which the activated macrophage can exert a selective effect on its extracellular environment.

PubMed Disclaimer

Similar articles

• In vitro synthesis and secretion of lysozyme by mononuclear phagocytes.
  Gordon S, Todd J, Cohn ZA. Gordon S, et al. J Exp Med. 1974 May 1;139(5):1228-48. doi: 10.1084/jem.139.5.1228. J Exp Med. 1974. PMID: 4825244 Free PMC article.
• Secretion of plasminogen activator by stimulated macrophages.
  Unkeless JC, Gordon S, Reich E. Unkeless JC, et al. J Exp Med. 1974 Apr 1;139(4):834-50. doi: 10.1084/jem.139.4.834. J Exp Med. 1974. PMID: 4816302 Free PMC article.
• Macrophage plasminogen activator: induction by products of activated lymphoid cells.
  Vassalli JD, Reich E. Vassalli JD, et al. J Exp Med. 1977 Feb 1;145(2):429-37. doi: 10.1084/jem.145.2.429. J Exp Med. 1977. PMID: 833546 Free PMC article.
• Macrophage proteases and rheumatic diseases: regulation of plasminogen activator by thymus-derived lymphocytes.
  Gordon S, Newman W, Bloom B. Gordon S, et al. Agents Actions. 1978 Jan;8(1-2):19-26. doi: 10.1007/BF01972397. Agents Actions. 1978. PMID: 345780 Review.
• The macrophage as a secretory cell in chronic inflammation.
  Davies P, Allison AC. Davies P, et al. Agents Actions. 1976 Feb;6(1-3):60-74. doi: 10.1007/BF01972187. Agents Actions. 1976. PMID: 181971 Review.

Cited by

• The role of antigen-presenting cells in the pathogenesis of COVID-19.
  Farzi R, Aghbash PS, Eslami N, Azadi A, Shamekh A, Hemmat N, Entezari-Maleki T, Baghi HB. Farzi R, et al. Pathol Res Pract. 2022 May;233:153848. doi: 10.1016/j.prp.2022.153848. Epub 2022 Mar 23. Pathol Res Pract. 2022. PMID: 35338971 Free PMC article. Review.
• Monocyte activation in systemic Covid-19 infection: Assay and rationale.
  Martinez FO, Combes TW, Orsenigo F, Gordon S. Martinez FO, et al. EBioMedicine. 2020 Sep;59:102964. doi: 10.1016/j.ebiom.2020.102964. Epub 2020 Aug 30. EBioMedicine. 2020. PMID: 32861199 Free PMC article. Review.
• Activated macrophages for treating skin ulceration: gene expression in human monocytes after hypo-osmotic shock.
  Frenkel O, Shani E, Ben-Bassat I, Brok-Simoni F, Rozenfeld-Granot G, Kajakaro G, Rechavi G, Amariglio N, Shinar E, Danon D. Frenkel O, et al. Clin Exp Immunol. 2002 Apr;128(1):59-66. doi: 10.1046/j.1365-2249.2002.01630.x. Clin Exp Immunol. 2002. PMID: 11982591 Free PMC article.
• Activation of human monocytes/macrophages by hypo-osmotic shock.
  Frenkel O, Shani E, Ben-Bassat I, Brok-Simoni F, Shinar E, Danon D. Frenkel O, et al. Clin Exp Immunol. 2001 Apr;124(1):103-9. doi: 10.1046/j.1365-2249.2001.01496.x. Clin Exp Immunol. 2001. PMID: 11359448 Free PMC article.
• Zanvil Alexander Cohn 1926-1993.
  Steinman RM, Moberg CL. Steinman RM, et al. J Exp Med. 1994 Jan 1;179(1):1-30. doi: 10.1084/jem.179.1.1. J Exp Med. 1994. PMID: 8270858 Free PMC article.

References

1. 1. Lab Invest. 1968 Dec;19(6):584-90 - PubMed
2. 1. Adv Immunol. 1969;10:145-227 - PubMed
3. 1. J Exp Med. 1970 Jun 1;131(6):1239-60 - PubMed
4. 1. Eur J Biochem. 1971 Mar 1;19(1):143-52 - PubMed
5. 1. Nat New Biol. 1971 Jul 21;232(29):76-8 - PubMed

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Europe PubMed Central
  • Ovid Technologies, Inc.
  • PubMed Central
  • Silverchair Information Systems

• Other Literature Sources

  • The Lens - Patent Citations Database