Extracellular matrix derived from Trypanosoma cruzi infected endothelial cells directs phenotypic expression

Stephen A. Morris, Murray Wittner, Louis M. Weiss, Victor Bernard Hatcher, Herbert B. Tanowitz, John P. Bilezikian, Portia B. Gordon

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Infection of confluent human umbilical vein endothelial cells by the parasite Trypanosoma cruzi results in the appearance of an altered heparan sulfate proteoglycan (HSPG) isolated from the extracellular matrix of infected endothelial cells (ECMi). HSPG from ECMi differed from HSPG obtained from the extracellular matrix of uninfected endothelial cells (ECMu) by virtue of an 8-10-fold increase in sulfation and a different elution pattern using DEAE Sepharose chromatography. Analysis of the HSPG that binds to acidic fibroblast growth factor (aFGF) revealed that infection increased the proportion of HSPG that binds to aFGF by 35%. Heparitinase and alkaline borohydride treatment of aFGF-binding HSPG and Chromatographic resolution on Sepharose CL4B column revealed an infection-associated 10-fold increase in sulfation of the GAG side chain with no significant change in the migration of the core protein. In addition, the aFGF binding HSPG isolated from ECMi demonstrated a markedly attenuated synergistic mitogenic activity with aFGF in a cell proliferation assay. All of the infection associated changes in HSPG could be demonstrated in HSPG obtained from uninfected endothelial cell cultures grown on ECMi. Hence, the ECMi is associated with signals capable of modulating the ECM associated metabolism of uninfected endothelial cells. This facility of ECMi was also shown to extend to patterns of Gs protein synthesis as revealed by Western blot analysis. The observation that the ECM produced by infected endothelial cells can direct the synthetic patterns of uninfected endothelial cells in a manner uniquely observed in infected endothelial cells suggests a plausible pathway by which infection of only a few cells can ultimately result in the coordinate responses of neighboring uninfected cells.

Original languageEnglish (US)
Pages (from-to)340-346
Number of pages7
JournalJournal of Cellular Physiology
Volume145
Issue number2
StatePublished - Nov 1990

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Trypanosoma cruzi
Endothelial cells
Heparan Sulfate Proteoglycans
Extracellular Matrix
Endothelial Cells
Fibroblast Growth Factor 1
Infection
Military electronic countermeasures
heparitinsulfate lyase
Sepharose
Borohydrides
Agarose Chromatography
Human Umbilical Vein Endothelial Cells
Cell proliferation
Chromatography
Cell culture
Metabolism
Parasites
Proteins
Assays

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Extracellular matrix derived from Trypanosoma cruzi infected endothelial cells directs phenotypic expression. / Morris, Stephen A.; Wittner, Murray; Weiss, Louis M.; Hatcher, Victor Bernard; Tanowitz, Herbert B.; Bilezikian, John P.; Gordon, Portia B.

In: Journal of Cellular Physiology, Vol. 145, No. 2, 11.1990, p. 340-346.

Research output: Contribution to journalArticle

Morris, Stephen A. ; Wittner, Murray ; Weiss, Louis M. ; Hatcher, Victor Bernard ; Tanowitz, Herbert B. ; Bilezikian, John P. ; Gordon, Portia B. / Extracellular matrix derived from Trypanosoma cruzi infected endothelial cells directs phenotypic expression. In: Journal of Cellular Physiology. 1990 ; Vol. 145, No. 2. pp. 340-346.
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abstract = "Infection of confluent human umbilical vein endothelial cells by the parasite Trypanosoma cruzi results in the appearance of an altered heparan sulfate proteoglycan (HSPG) isolated from the extracellular matrix of infected endothelial cells (ECMi). HSPG from ECMi differed from HSPG obtained from the extracellular matrix of uninfected endothelial cells (ECMu) by virtue of an 8-10-fold increase in sulfation and a different elution pattern using DEAE Sepharose chromatography. Analysis of the HSPG that binds to acidic fibroblast growth factor (aFGF) revealed that infection increased the proportion of HSPG that binds to aFGF by 35{\%}. Heparitinase and alkaline borohydride treatment of aFGF-binding HSPG and Chromatographic resolution on Sepharose CL4B column revealed an infection-associated 10-fold increase in sulfation of the GAG side chain with no significant change in the migration of the core protein. In addition, the aFGF binding HSPG isolated from ECMi demonstrated a markedly attenuated synergistic mitogenic activity with aFGF in a cell proliferation assay. All of the infection associated changes in HSPG could be demonstrated in HSPG obtained from uninfected endothelial cell cultures grown on ECMi. Hence, the ECMi is associated with signals capable of modulating the ECM associated metabolism of uninfected endothelial cells. This facility of ECMi was also shown to extend to patterns of Gs protein synthesis as revealed by Western blot analysis. The observation that the ECM produced by infected endothelial cells can direct the synthetic patterns of uninfected endothelial cells in a manner uniquely observed in infected endothelial cells suggests a plausible pathway by which infection of only a few cells can ultimately result in the coordinate responses of neighboring uninfected cells.",
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