Skip to main content
NCBI home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1990 May;136(5):1125–1135.

Bartonella bacilliformis stimulates endothelial cells in vitro and is angiogenic in vivo.

F U Garcia 1, J Wojta 1, K N Broadley 1, J M Davidson 1, R L Hoover 1
PMCID: PMC1877437  PMID: 1693472

Abstract

Bartonellosis, a biphasic disease caused by motile intracellular bacteria, produces in its tissue phase a characteristic dermal eruption (Verruga peruana) resulting from a pronounced endothelial cell proliferation. Bacteria are found in the interstitium and within the cytoplasm of endothelial cells (Rocha-Lima inclusion). The aim of this study was to determine if Bartonella bacilliformis produce a substance(s) that might be responsible for the vascular proliferation seen in the Verruga. This was assessed in an in vitro system using human endothelial cells and measuring proliferation as well as production of tissue type plasminogen activator after exposure to the endothelial cultures to B. bacilliformis extracts. Our results indicate that B. bacilliformis possess an activity that stimulates endothelial cell proliferation up to three times that of control. The factor(s) is specific for endothelial cells, heat sensitive, larger than 12 to 14 kd, not enhanced by heparin, has no affinity for heparin, and is precipitated by 45% ammonium sulfate. In addition, the B. bacilliformis extracts stimulate production of t-PA antigen in a concentration-dependent fashion. This activity is also heat sensitive and not lost after dialysis (12 to 14 kd). B. bacilliformis extracts, however, do not increase the production of plasminogen activator inhibitor. It was also determined that B. bacilliformis extracts stimulate the formation of new blood vessels in an in vivo model for angiogenesis. These results describe a bacterial factor(s) that stimulates two important steps in the development of new blood vessels in vitro, as well as the formation of new blood vessels in vivo. Determining the mechanism of action, combined with a complete characterization of this factor(s), may help in understanding the pathogenesis not only of the Verruga and angiogenesis in general but also the recently described Cat-Scratch-associated epithelioid hemangiomas in patients with AIDS and Kaposi sarcoma.

Full text

PDF
1125

Images in this article

1131Figure 7
on p.1131

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arias-Stella J., Lieberman P. H., Erlandson R. A., Arias-Stella J., Jr Histology, immunohistochemistry, and ultrastructure of the verruga in Carrion's disease. Am J Surg Pathol. 1986 Sep;10(9):595–610. doi: 10.1097/00000478-198609000-00002. [DOI] [PubMed] [Google Scholar]
  2. Arias-Stella J., Lieberman P. H., Garcia-Caceres U., Erlandson R. A., Kruger H., Arias-Stella J., Jr Verruga peruana mimicking malignant neoplasms. Am J Dermatopathol. 1987 Aug;9(4):279–291. doi: 10.1097/00000372-198708000-00001. [DOI] [PubMed] [Google Scholar]
  3. Ausprunk D. H., Folkman J. Migration and proliferation of endothelial cells in preformed and newly formed blood vessels during tumor angiogenesis. Microvasc Res. 1977 Jul;14(1):53–65. doi: 10.1016/0026-2862(77)90141-8. [DOI] [PubMed] [Google Scholar]
  4. Benson L. A., Kar S., McLaughlin G., Ihler G. M. Entry of Bartonella bacilliformis into erythrocytes. Infect Immun. 1986 Nov;54(2):347–353. doi: 10.1128/iai.54.2.347-353.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Broadley K. N., Aquino A. M., Hicks B., Ditesheim J. A., McGee G. S., Demetriou A. A., Woodward S. C., Davidson J. M. The diabetic rat as an impaired wound healing model: stimulatory effects of transforming growth factor-beta and basic fibroblast growth factor. Biotechnol Ther. 1989 1990;1(1):55–68. [PubMed] [Google Scholar]
  6. CUADRA M. Salmonellosis complication in human bartonellosis. Tex Rep Biol Med. 1956;14(2):97–113. [PubMed] [Google Scholar]
  7. Cockerell C. J., Whitlow M. A., Webster G. F., Friedman-Kien A. E. Epithelioid angiomatosis: a distinct vascular disorder in patients with the acquired immunodeficiency syndrome or AIDS-related complex. Lancet. 1987 Sep 19;2(8560):654–656. doi: 10.1016/s0140-6736(87)92442-1. [DOI] [PubMed] [Google Scholar]
  8. Fett J. W., Strydom D. J., Lobb R. R., Alderman E. M., Bethune J. L., Riordan J. F., Vallee B. L. Isolation and characterization of angiogenin, an angiogenic protein from human carcinoma cells. Biochemistry. 1985 Sep 24;24(20):5480–5486. doi: 10.1021/bi00341a030. [DOI] [PubMed] [Google Scholar]
  9. Garcia F. U. Tissue reaction in bartonellosis may suggest Kaposi's sarcoma. Arch Pathol Lab Med. 1985 Aug;109(8):703–704. [PubMed] [Google Scholar]
  10. Gross J. L., Moscatelli D., Jaffe E. A., Rifkin D. B. Plasminogen activator and collagenase production by cultured capillary endothelial cells. J Cell Biol. 1982 Dec;95(3):974–981. doi: 10.1083/jcb.95.3.974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. HERRER A. Carrión's disease. II. Presence of Bartonella bacilliformis in the peripheral blood of patients with the benign form. Am J Trop Med Hyg. 1953 Jul;2(4):645–649. [PubMed] [Google Scholar]
  12. Hanss M., Collen D. Secretion of tissue-type plasminogen activator and plasminogen activator inhibitor by cultured human endothelial cells: modulation by thrombin, endotoxin, and histamine. J Lab Clin Med. 1987 Jan;109(1):97–104. [PubMed] [Google Scholar]
  13. Hoover R. L., Briggs R. T., Karnovsky M. J. The adhesive interaction between polymorphonuclear leukocytes and endothelial cells in vitro. Cell. 1978 Jun;14(2):423–428. doi: 10.1016/0092-8674(78)90127-7. [DOI] [PubMed] [Google Scholar]
  14. Hubbard B. D., Lazarides E. Copurification of actin and desmin from chicken smooth muscle and their copolymerization in vitro to intermediate filaments. J Cell Biol. 1979 Jan;80(1):166–182. doi: 10.1083/jcb.80.1.166. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Johnson A. R. Human pulmonary endothelial cells in culture. Activities of cells from arteries and cells from veins. J Clin Invest. 1980 Apr;65(4):841–850. doi: 10.1172/JCI109736. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. LeBoit P. E., Berger T. G., Egbert B. M., Yen T. S., Stoler M. H., Bonfiglio T. A., Strauchen J. A., English C. K., Wear D. J. Epithelioid haemangioma-like vascular proliferation in AIDS: manifestation of cat scratch disease bacillus infection? Lancet. 1988 Apr 30;1(8592):960–963. doi: 10.1016/s0140-6736(88)91779-5. [DOI] [PubMed] [Google Scholar]
  18. Maciag T., Hoover G. A., Weinstein R. High and low molecular weight forms of endothelial cell growth factor. J Biol Chem. 1982 May 25;257(10):5333–5336. [PubMed] [Google Scholar]
  19. Maciag T., Mehlman T., Friesel R., Schreiber A. B. Heparin binds endothelial cell growth factor, the principal endothelial cell mitogen in bovine brain. Science. 1984 Aug 31;225(4665):932–935. doi: 10.1126/science.6382607. [DOI] [PubMed] [Google Scholar]
  20. Marquardt H., Hunkapiller M. W., Hood L. E., Todaro G. J. Rat transforming growth factor type 1: structure and relation to epidermal growth factor. Science. 1984 Mar 9;223(4640):1079–1082. doi: 10.1126/science.6320373. [DOI] [PubMed] [Google Scholar]
  21. Mignatti P., Tsuboi R., Robbins E., Rifkin D. B. In vitro angiogenesis on the human amniotic membrane: requirement for basic fibroblast growth factor-induced proteinases. J Cell Biol. 1989 Feb;108(2):671–682. doi: 10.1083/jcb.108.2.671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Nickoloff B. J., Griffiths C. E. Factor XIIIa-expressing dermal dendrocytes in AIDS-associated cutaneous Kaposi's sarcomas. Science. 1989 Mar 31;243(4899):1736–1737. doi: 10.1126/science.2564703. [DOI] [PubMed] [Google Scholar]
  23. Recavarren S., Lumbreras H. Pathogenesis of the verruga of Carrion's disease. Ultrastructural studies. Am J Pathol. 1972 Mar;66(3):461–470. [PMC free article] [PubMed] [Google Scholar]
  24. Ryan J. W., Chung A., Martin L. C., Ryan U. S. New substrates for the radioassay of angiotensin converting enzyme of endothelial cells in culture. Tissue Cell. 1978;10(3):555–562. doi: 10.1016/s0040-8166(16)30348-2. [DOI] [PubMed] [Google Scholar]
  25. Sacks T., Moldow C. F., Craddock P. R., Bowers T. K., Jacob H. S. Oxygen radicals mediate endothelial cell damage by complement-stimulated granulocytes. An in vitro model of immune vascular damage. J Clin Invest. 1978 May;61(5):1161–1167. doi: 10.1172/JCI109031. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Speiser W., Wojta J., Korninger C., Kirchheimer J. C., Zazgornik J., Binder B. R. Enhanced fibrinolysis caused by tissue plasminogen activator release in hemodialysis. Kidney Int. 1987 Aug;32(2):280–283. doi: 10.1038/ki.1987.204. [DOI] [PubMed] [Google Scholar]
  27. Stein O., Stein Y. Bovine aortic endothelial cells display macrophage-like properties towards acetylated 125I-labelled low density lipoprotein. Biochim Biophys Acta. 1980 Dec 5;620(3):631–635. doi: 10.1016/0005-2760(80)90155-1. [DOI] [PubMed] [Google Scholar]
  28. Stoler M. H., Bonfiglio T. A., Steigbigel R. T., Pereira M. An atypical subcutaneous infection associated with acquired immune deficiency syndrome. Am J Clin Pathol. 1983 Nov;80(5):714–718. doi: 10.1093/ajcp/80.5.714. [DOI] [PubMed] [Google Scholar]
  29. Tucker R. F., Shipley G. D., Moses H. L., Holley R. W. Growth inhibitor from BSC-1 cells closely related to platelet type beta transforming growth factor. Science. 1984 Nov 9;226(4675):705–707. doi: 10.1126/science.6093254. [DOI] [PubMed] [Google Scholar]
  30. URTEAGA O., PAYNE E. H. Treatment of the acute febrile phase of Carrión's disease with chloramphenicol. Am J Trop Med Hyg. 1955 May;4(3):507–511. doi: 10.4269/ajtmh.1955.4.507. [DOI] [PubMed] [Google Scholar]
  31. Wahl S. M., Hunt D. A., Wakefield L. M., McCartney-Francis N., Wahl L. M., Roberts A. B., Sporn M. B. Transforming growth factor type beta induces monocyte chemotaxis and growth factor production. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5788–5792. doi: 10.1073/pnas.84.16.5788. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Walker T. S., Winkler H. H. Bartonella bacilliformis: colonial types and erythrocyte adherence. Infect Immun. 1981 Jan;31(1):480–486. doi: 10.1128/iai.31.1.480-486.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Walther B. T., Ohman R., Roseman S. A quantitative assay for intercellular adhesion. Proc Natl Acad Sci U S A. 1973 May;70(5):1569–1573. doi: 10.1073/pnas.70.5.1569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Wojta J., Turcu L., Wagner O. F., Korninger C., Binder B. R. Evaluation of fibrinolytic capacity by a combined assay system for tissue-type plasminogen activator antigen and function using monoclonal anti-tissue-type plasminogen activator antibodies. J Lab Clin Med. 1987 Jun;109(6):665–671. [PubMed] [Google Scholar]
  35. Woodward S. C., Herrmann J. B. Stimulation of fibroplasia in rats by bovine cartilage powder. Arch Surg. 1968 Feb;96(2):189–199. doi: 10.1001/archsurg.1968.01330200027005. [DOI] [PubMed] [Google Scholar]
  36. Yen A., Braverman I. M. Ultrastructure of the human dermal microcirculation: the horizontal plexus of the papillary dermis. J Invest Dermatol. 1976 Mar;66(3):131–142. doi: 10.1111/1523-1747.ep12481678. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES