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. 1985 Oct;76(4):1382–1390. doi: 10.1172/JCI112114

Viral infection of vascular endothelial cells alters production of colony-stimulating activity.

S L Gerson, H M Friedman, D B Cines
PMCID: PMC424082  PMID: 2414319

Abstract

Viral infections in humans are frequently associated with granulocytopenia and/or granulocytosis. Such changes in myelopoiesis could result from infection of the granulocyte-macrophage colony-forming cell (CFC-GM) or changes in the production of colony-stimulating activity (CSA). Endothelial cells are a known source of CSA and may be transiently or persistently infected during a number of viral infections, including infection with herpes simplex virus type I (HSV-I) and measles virus. Therefore, we examined the effect of endothelial cell infection with these two viruses on the production of CSA. Uninfected passaged endothelial cells produce CSA when stimulated by the continual presence of a factor present in medium conditioned by peripheral blood monocytes (MCM). Within 4 h of infection with HSV-I, endothelial cells no longer produced CSA in response to MCM. In contrast, measles virus infection induced CSA production by passaged endothelial cells even in the absence of MCM. Measles virus-induced CSA production was maximal at 24 h and required the presence of live virus within the endothelial cells. The effects of HSV-I and measles virus on CSA production were not dependent on alterations in the production of alpha- or gamma-interferon by the infected endothelial cells. Infection with HSV-I did not stimulate endothelial cells to release any detectable interferon. In contrast, the supernatants of the measles-infected cells contained only beta-interferon, a known inhibitor of CFC-GM development. These studies suggest that CSA production by endothelial cells is directly altered by infection with HSV-I and measles virus. An alteration in CSA production might contribute to changes in myelopoiesis that frequently accompany viral infection in humans.

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Selected References

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  1. Abrahm J. L., Smiley R. Modification of normal human myelopoiesis by 12-0 tetradecanoylphorbol-13-acetate (TPA). Blood. 1981 Dec;58(6):1119–1126. [PubMed] [Google Scholar]
  2. Ascensao J. L., Vercellotti G. M., Jacob H. S., Zanjani E. D. Role of endothelial cells in human hematopoiesis: modulation of mixed colony growth in vitro. Blood. 1984 Mar;63(3):553–558. [PubMed] [Google Scholar]
  3. Bagby G. C., Jr, Lawrence H. J., Neerhout R. C. T-lymphocyte--mediated granulopoietic failure. In vitro identification of prednisone-responsive patients. N Engl J Med. 1983 Nov 3;309(18):1073–1078. doi: 10.1056/NEJM198311033091801. [DOI] [PubMed] [Google Scholar]
  4. Bagby G. C., Jr, McCall E., Bergstrom K. A., Burger D. A monokine regulates colony-stimulating activity production by vascular endothelial cells. Blood. 1983 Sep;62(3):663–668. [PubMed] [Google Scholar]
  5. Bagby G. C., Jr, McCall E., Layman D. L. Regulation of colony-stimulating activity production. Interactions of fibroblasts, mononuclear phagocytes, and lactoferrin. J Clin Invest. 1983 Feb;71(2):340–344. doi: 10.1172/JCI110774. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bagby G. C., Jr, Rigas V. D., Bennett R. M., Vandenbark A. A., Garewal H. S. Interaction of lactoferrin, monocytes, and T lymphocyte subsets in the regulation of steady-state granulopoiesis in vitro. J Clin Invest. 1981 Jul;68(1):56–63. doi: 10.1172/JCI110254. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Black F. L., Sheridan S. R. Blood leukocyte response to live measles vaccine. Am J Dis Child. 1967 Mar;113(3):301–304. doi: 10.1001/archpedi.1967.02090180061002. [DOI] [PubMed] [Google Scholar]
  8. Booyse F. M., Quarfoot A. J., Chediak J., Stemerman M. B., Maciag T. Characterization and properties of cultured human von Willebrand umbilical vein endothelial cells. Blood. 1981 Oct;58(4):788–796. [PubMed] [Google Scholar]
  9. Broxmeyer H. E., Bognacki J., Ralph P., Dörner M. H., Lu L., Castro-Malaspina H. Monocyte-macrophage-derived acidic isoferritins: normal feedback regulators of granulocyte-macrophage progenitor cells in vitro. Blood. 1982 Sep;60(3):595–607. [PubMed] [Google Scholar]
  10. Broxmeyer H. E., Lu L., Platzer E., Feit C., Juliano L., Rubin B. Y. Comparative analysis of the influences of human gamma, alpha and beta interferons on human multipotential (CFU-GEMM), erythroid (BFU-E) and granulocyte-macrophage (CFU-GM) progenitor cells. J Immunol. 1983 Sep;131(3):1300–1305. [PubMed] [Google Scholar]
  11. Burgess A. W., Metcalf D. The nature and action of granulocyte-macrophage colony stimulating factors. Blood. 1980 Dec;56(6):947–958. [PubMed] [Google Scholar]
  12. Carter R. L. Granulocyte changes in infectious mononucleosis. J Clin Pathol. 1966 May;19(3):279–283. doi: 10.1136/jcp.19.3.279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Cines D. B., Lyss A. P., Bina M., Corkey R., Kefalides N. A., Friedman H. M. Fc and C3 receptors induced by herpes simplex virus on cultured human endothelial cells. J Clin Invest. 1982 Jan;69(1):123–128. doi: 10.1172/JCI110422. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Cines D. B., Lyss A. P., Reeber M., Bina M., DeHoratius R. J. Presence of complement-fixing anti-endothelial cell antibodies in systemic lupus erythematosus. J Clin Invest. 1984 Mar;73(3):611–625. doi: 10.1172/JCI111251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Curzon P. G., Muers M. F., Rajah S. M. Aplastic anaemia associated with influenza A infection. Scand J Haematol. 1983 Mar;30(3):232–234. doi: 10.1111/j.1600-0609.1983.tb01482.x. [DOI] [PubMed] [Google Scholar]
  16. Davis L. R. Aplastic crises in haemolytic anaemias: the role of a parvovirus-like agent. Br J Haematol. 1983 Nov;55(3):391–393. doi: 10.1111/j.1365-2141.1983.tb02153.x. [DOI] [PubMed] [Google Scholar]
  17. Dexter T. M., Spooncer E., Toksoz D., Lajtha L. G. The role of cells and their products in the regulation of in vitro stem cell proliferation and granulocyte development. J Supramol Struct. 1980;13(4):513–524. doi: 10.1002/jss.400130410. [DOI] [PubMed] [Google Scholar]
  18. Fenwick M. L., Clark J. Early and delayed shut-off of host protein synthesis in cells infected with herpes simplex virus. J Gen Virol. 1982 Jul;61(Pt 50):121–125. doi: 10.1099/0022-1317-61-1-121. [DOI] [PubMed] [Google Scholar]
  19. Fenwick M. L., Walker M. J. Suppression of the synthesis of cellular macromolecules by herpes simplex virus. J Gen Virol. 1978 Oct;41(1):37–51. doi: 10.1099/0022-1317-41-1-37. [DOI] [PubMed] [Google Scholar]
  20. Friedman H. M., Macarak E. J., MacGregor R. R., Wolfe J., Kefalides N. A. Virus infection of endothelial cells. J Infect Dis. 1981 Feb;143(2):266–273. doi: 10.1093/infdis/143.2.266. [DOI] [PubMed] [Google Scholar]
  21. Gerson S. L., Cooper R. A. Release of granulocyte-specific colony-stimulating activity by human bone marrow exposed to phorbol esters. Blood. 1984 Apr;63(4):878–885. [PubMed] [Google Scholar]
  22. Gimbrone M. A., Jr, Cotran R. S., Folkman J. Human vascular endothelial cells in culture. Growth and DNA synthesis. J Cell Biol. 1974 Mar;60(3):673–684. doi: 10.1083/jcb.60.3.673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Hagler L., Pastore R. A., Bergin J. J., Wrensch M. R. Aplastic anemia following viral hepatitis: report of two fatal cases and literature review. Medicine (Baltimore) 1975 Mar;54(2):139–164. [PubMed] [Google Scholar]
  24. Iscove N. N., Roitsch C. A., Williams N., Guilbert L. J. Molecules stimulating early red cell, granulocyte, macrophage, and megakaryocyte precursors in culture: similarity in size, hydrophobicity, and charge. J Cell Physiol Suppl. 1982;1:65–78. doi: 10.1002/jcp.1041130412. [DOI] [PubMed] [Google Scholar]
  25. Jaffe E. A., Nachman R. L., Becker C. G., Minick C. R. Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J Clin Invest. 1973 Nov;52(11):2745–2756. doi: 10.1172/JCI107470. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Kimura N., Niho Y., Yanase T. A high level of colony-stimulating activity in a lung cancer patient with extensive leucocytosis, and the establishment of a CSA producing cell line (KONT). Scand J Haematol. 1982 May;28(5):417–424. doi: 10.1111/j.1600-0609.1982.tb00547.x. [DOI] [PubMed] [Google Scholar]
  27. Klimpel G. R., Fleischmann W. R., Jr, Klimpel K. D. Gamma interferon (IFN gamma) and IFN alpha/beta suppress murine myeloid colony formation (CFU-C)N: magnitude of suppression is dependent upon level of colony-stimulating factor (CSF). J Immunol. 1982 Jul;129(1):76–80. [PubMed] [Google Scholar]
  28. Koury M. J., Pragnell I. B. Retroviruses induce granulocyte-macrophage colony stimulating activity in fibroblasts. Nature. 1982 Oct 14;299(5884):638–640. doi: 10.1038/299638a0. [DOI] [PubMed] [Google Scholar]
  29. Lu L., Broxmeyer H. E., Moore M. A., Sheridan A. P., Gentile P. Abnormalities in myelopoietic regulatory interactions with acidic isoferritins and lactoferrin in mice infected with Friend virus complex: association with altered expression of Ia antigens on effector and responding cells. Blood. 1985 Jan;65(1):91–99. [PubMed] [Google Scholar]
  30. MacGregor R. R., Friedman H. M., Macarak E. J., Kefalides N. A. Virus infection of endothelial cells increases granulocyte adherence. J Clin Invest. 1980 Jun;65(6):1469–1477. doi: 10.1172/JCI109811. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Maciag T., Cerundolo J., Ilsley S., Kelley P. R., Forand R. An endothelial cell growth factor from bovine hypothalamus: identification and partial characterization. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5674–5678. doi: 10.1073/pnas.76.11.5674. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Metcalf D., Johnson G. R., Burgess A. W. Direct stimulation by purified GM-CSF of the proliferation of multipotential and erythroid precursor cells. Blood. 1980 Jan;55(1):138–147. [PubMed] [Google Scholar]
  33. Montesano R., Orci L., Vassalli P. Human endothelial cell cultures: phenotypic modulation by leukocyte interleukins. J Cell Physiol. 1985 Mar;122(3):424–434. doi: 10.1002/jcp.1041220313. [DOI] [PubMed] [Google Scholar]
  34. Moss D. J., Rickinson A. B., Pope J. H. Long-term T-cell-mediated immunity to Epstein-Barr virus in man. III. Activation of cytotoxic T cells in virus-infected leukocyte cultures. Int J Cancer. 1979 May 15;23(5):618–625. doi: 10.1002/ijc.2910230506. [DOI] [PubMed] [Google Scholar]
  35. Neumann H. A., Fauser A. A. Effect of interferon on pluripotent hemopoietic progenitors (CFU-GEMM) derived from human bone marrow. Exp Hematol. 1982 Aug;10(7):587–590. [PubMed] [Google Scholar]
  36. Pelus L. M., Broxmeyer H. E., Kurland J. I., Moore M. A. Regulation of macrophage and granulocyte proliferation. Specificities of prostaglandin E and lactoferrin. J Exp Med. 1979 Aug 1;150(2):277–292. doi: 10.1084/jem.150.2.277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Perussia B., Dayton E. T., Lazarus R., Fanning V., Trinchieri G. Immune interferon induces the receptor for monomeric IgG1 on human monocytic and myeloid cells. J Exp Med. 1983 Oct 1;158(4):1092–1113. doi: 10.1084/jem.158.4.1092. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Petursson S. R., Chervenick P. A., Wu B. Megakaryocytopoiesis and granulopoiesis after murine cytomegalovirus infection. J Lab Clin Med. 1984 Sep;104(3):381–390. [PubMed] [Google Scholar]
  39. Pober J. S., Gimbrone M. A., Jr, Cotran R. S., Reiss C. S., Burakoff S. J., Fiers W., Ault K. A. Ia expression by vascular endothelium is inducible by activated T cells and by human gamma interferon. J Exp Med. 1983 Apr 1;157(4):1339–1353. doi: 10.1084/jem.157.4.1339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Quesenberry P. J., Gimbrone M. A., Jr Vascular endothelium as a regulator of granulopoiesis: production of colony-stimulating activity by cultured human endothelial cells. Blood. 1980 Dec;56(6):1060–1067. [PubMed] [Google Scholar]
  41. Schooley R. T., Haynes B. F., Grouse J., Payling-Wright C., Fauci A. S., Dolin R. Development of suppressor T lymphocytes for Epstein-Barr virus-induced B-lymphocyte outgrowth during acute infectious mononucleosis: assessment by two quantitative systems. Blood. 1981 Mar;57(3):510–517. [PubMed] [Google Scholar]
  42. Schooley R. T., Hirsch M. S., Colvin R. B., Cosimi A. B., Tolkoff-Rubin N. E., McCluskey R. T., Burton R. C., Russell P. S., Herrin J. T., Delmonico F. L. Association of herpesvirus infections with T-lymphocyte-subset alterations, glomerulopathy, and opportunistic infections after renal transplantation. N Engl J Med. 1983 Feb 10;308(6):307–313. doi: 10.1056/NEJM198302103080603. [DOI] [PubMed] [Google Scholar]
  43. Schrader J. W., Clark-Lewis I. A T cell-derived factor stimulating multipotential hemopoietic stem cells: molecular weight and distinction from T cell growth factor and T cell-derived granulocyte-macrophage colony-stimulating factor. J Immunol. 1982 Jul;129(1):30–35. [PubMed] [Google Scholar]
  44. Trinchieri G., Matsumoto-Kobayashi M., Clark S. C., Seehra J., London L., Perussia B. Response of resting human peripheral blood natural killer cells to interleukin 2. J Exp Med. 1984 Oct 1;160(4):1147–1169. doi: 10.1084/jem.160.4.1147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Verma D. S., Spitzer G., Zander A. R., Fisher R., McCredie K. B., Dicke K. A. T lymphocyte and monocyte-macrophage interaction in colony-stimulating activity elaboration in man. Blood. 1979 Dec;54(6):1376–1383. [PubMed] [Google Scholar]
  46. Young N. S., Mortimer P. P., Moore J. G., Humphries R. K. Characterization of a virus that causes transient aplastic crisis. J Clin Invest. 1984 Jan;73(1):224–230. doi: 10.1172/JCI111195. [DOI] [PMC free article] [PubMed] [Google Scholar]

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