HIV-1 infection of microvascular endothelial cells facilitates growth of aids associated b cell lymphomas

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Abstract

AIDS patients have a high incidence of aggressive B cell nonHodgkin's lymphomas (AIDS-NHL) that involve extranodal sites including bone marrow. Since malignant B cells in AIDS-NHL are not directly infected by HIV, interaction of B cells with HIV-infected accessory cells at extranodal sites may contribute to development and unique localization of such lymphomas. Using bone marrow stromal cultures enriched for microvascular endothelial cells (MVEC), we have demonstrated that bone marrow MVEC are naturally infected by HIV in vivo. (Moses A.V. et al. Blood, 1996). MVEC-enriched stromal culture derived from an HIV-seropositive patient with EBV-negative Burkitt's lymphoma gave rise to the spontaneous and sustained in vitro outgrowth of stromal dependent B cells containing the Burkitt's t(8;14) translocation. Moreover, ex vivo HIV infection of MVEC-enriched stroma from HIV-seronegative lymphoma patients induced outgrowths of autologous malignant B cells. We also found that adherence of B lymphoma cells to brain MVEC was significantly enhanced upon HIV infection and that while antibody blocking experiments demonstrated that the VCAM-1/VLA-4 interaction was involved, HIV infection of MVEC had no effect on the expression of VCAM1. However, while brain MVEC expressed CD40 at low levels constitutively, HIV infection significantly enhanced CD40 expression and, more importantly, an agonistic CD40 monoclonal antibody (mAb) triggered expression of VCAM-1 on infected brain MVEC but not mock-infected MVEC We suggest that HIV infection of MVEC in extranodal sites may be uniquely supportive of adhesion and outgrowth of lymphoma cells, in part, through a mechanism involving first induction of CD40 in MVEC by HIV-1 and secondly CD40L induced VCAM-1 expression by these cells.

Original languageEnglish (US)
Pages (from-to)732
Number of pages1
JournalExperimental Hematology
Volume25
Issue number8
StatePublished - 1997

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HIV Infections
HIV-1
Lymphoma
Endothelial Cells
Growth
HIV
Vascular Cell Adhesion Molecule-1
B-Lymphocytes
Acquired Immunodeficiency Syndrome
Bone Marrow
B-Cell Lymphoma
Brain
Integrin alpha4beta1
CD40 Ligand
Blocking Antibodies
Burkitt Lymphoma
Human Herpesvirus 4
Non-Hodgkin's Lymphoma
Monoclonal Antibodies
Incidence

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation

Cite this

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title = "HIV-1 infection of microvascular endothelial cells facilitates growth of aids associated b cell lymphomas",
abstract = "AIDS patients have a high incidence of aggressive B cell nonHodgkin's lymphomas (AIDS-NHL) that involve extranodal sites including bone marrow. Since malignant B cells in AIDS-NHL are not directly infected by HIV, interaction of B cells with HIV-infected accessory cells at extranodal sites may contribute to development and unique localization of such lymphomas. Using bone marrow stromal cultures enriched for microvascular endothelial cells (MVEC), we have demonstrated that bone marrow MVEC are naturally infected by HIV in vivo. (Moses A.V. et al. Blood, 1996). MVEC-enriched stromal culture derived from an HIV-seropositive patient with EBV-negative Burkitt's lymphoma gave rise to the spontaneous and sustained in vitro outgrowth of stromal dependent B cells containing the Burkitt's t(8;14) translocation. Moreover, ex vivo HIV infection of MVEC-enriched stroma from HIV-seronegative lymphoma patients induced outgrowths of autologous malignant B cells. We also found that adherence of B lymphoma cells to brain MVEC was significantly enhanced upon HIV infection and that while antibody blocking experiments demonstrated that the VCAM-1/VLA-4 interaction was involved, HIV infection of MVEC had no effect on the expression of VCAM1. However, while brain MVEC expressed CD40 at low levels constitutively, HIV infection significantly enhanced CD40 expression and, more importantly, an agonistic CD40 monoclonal antibody (mAb) triggered expression of VCAM-1 on infected brain MVEC but not mock-infected MVEC We suggest that HIV infection of MVEC in extranodal sites may be uniquely supportive of adhesion and outgrowth of lymphoma cells, in part, through a mechanism involving first induction of CD40 in MVEC by HIV-1 and secondly CD40L induced VCAM-1 expression by these cells.",
author = "Ashlee Moses and M. Heneveld and Jay Nelson and Bagby, {G. G.}",
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AU - Moses, Ashlee

AU - Heneveld, M.

AU - Nelson, Jay

AU - Bagby, G. G.

PY - 1997

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N2 - AIDS patients have a high incidence of aggressive B cell nonHodgkin's lymphomas (AIDS-NHL) that involve extranodal sites including bone marrow. Since malignant B cells in AIDS-NHL are not directly infected by HIV, interaction of B cells with HIV-infected accessory cells at extranodal sites may contribute to development and unique localization of such lymphomas. Using bone marrow stromal cultures enriched for microvascular endothelial cells (MVEC), we have demonstrated that bone marrow MVEC are naturally infected by HIV in vivo. (Moses A.V. et al. Blood, 1996). MVEC-enriched stromal culture derived from an HIV-seropositive patient with EBV-negative Burkitt's lymphoma gave rise to the spontaneous and sustained in vitro outgrowth of stromal dependent B cells containing the Burkitt's t(8;14) translocation. Moreover, ex vivo HIV infection of MVEC-enriched stroma from HIV-seronegative lymphoma patients induced outgrowths of autologous malignant B cells. We also found that adherence of B lymphoma cells to brain MVEC was significantly enhanced upon HIV infection and that while antibody blocking experiments demonstrated that the VCAM-1/VLA-4 interaction was involved, HIV infection of MVEC had no effect on the expression of VCAM1. However, while brain MVEC expressed CD40 at low levels constitutively, HIV infection significantly enhanced CD40 expression and, more importantly, an agonistic CD40 monoclonal antibody (mAb) triggered expression of VCAM-1 on infected brain MVEC but not mock-infected MVEC We suggest that HIV infection of MVEC in extranodal sites may be uniquely supportive of adhesion and outgrowth of lymphoma cells, in part, through a mechanism involving first induction of CD40 in MVEC by HIV-1 and secondly CD40L induced VCAM-1 expression by these cells.

AB - AIDS patients have a high incidence of aggressive B cell nonHodgkin's lymphomas (AIDS-NHL) that involve extranodal sites including bone marrow. Since malignant B cells in AIDS-NHL are not directly infected by HIV, interaction of B cells with HIV-infected accessory cells at extranodal sites may contribute to development and unique localization of such lymphomas. Using bone marrow stromal cultures enriched for microvascular endothelial cells (MVEC), we have demonstrated that bone marrow MVEC are naturally infected by HIV in vivo. (Moses A.V. et al. Blood, 1996). MVEC-enriched stromal culture derived from an HIV-seropositive patient with EBV-negative Burkitt's lymphoma gave rise to the spontaneous and sustained in vitro outgrowth of stromal dependent B cells containing the Burkitt's t(8;14) translocation. Moreover, ex vivo HIV infection of MVEC-enriched stroma from HIV-seronegative lymphoma patients induced outgrowths of autologous malignant B cells. We also found that adherence of B lymphoma cells to brain MVEC was significantly enhanced upon HIV infection and that while antibody blocking experiments demonstrated that the VCAM-1/VLA-4 interaction was involved, HIV infection of MVEC had no effect on the expression of VCAM1. However, while brain MVEC expressed CD40 at low levels constitutively, HIV infection significantly enhanced CD40 expression and, more importantly, an agonistic CD40 monoclonal antibody (mAb) triggered expression of VCAM-1 on infected brain MVEC but not mock-infected MVEC We suggest that HIV infection of MVEC in extranodal sites may be uniquely supportive of adhesion and outgrowth of lymphoma cells, in part, through a mechanism involving first induction of CD40 in MVEC by HIV-1 and secondly CD40L induced VCAM-1 expression by these cells.

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