Infection of endothelium with E1-E4+, but not E1-E4-, adenovirus gene transfer vectors enhances leukocyte adhesion and migration by modulation of ICAM-1, VCAM-1, CD34, and chemokine expression

Shahin Rafii, Sergio Dias, Sarah Meeus, Koichi Hattori, Ramalingam Ramachandran, Fred Feuerback, Stefan Worgall, Neil R. Hackett, Ronald Crystal

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Intravascular introduction of replication-deficient adenoviral vectors (Advectors) provides an ideal model of delivery of transgenes for the treatment of various vascular abnormalities. On the basis of the knowledge that Advectors can induce inflammatory responses after intravascular administration, we speculated that cellular activation by Advector infection could directly modulate the endothelial cell (EC) adhesion molecule/chemokine expression repertoire. Infection of human umbilical vein ECs or bone marrow microvascular ECs with an E1-E4+ Advector resulted in the upregulation of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and CD34, but not E-selectin, P-selectin, CD36, CD13, CD44, HLA-DR or PECAM. Upregulation of ICAM-1, VCAM-1, and CD34 was apparent 12 hours after infection and persisted for weeks after infection. Selective induction of adhesion molecules was mediated by the presence of the E4 gene in the Advector, because infection of ECs with an E1-E4- Advector had no effect on adhesion molecule expression. ECs infected with E1-E4+ Advector, but not those infected with E1-E4- Advector, supported the adhesion of leukocytes. Monoclonal antibodies to ICAM-1 and VCAM-1 inhibited adhesion of leukocytes to E1-E4+-infected ECs. Infection of the ECs with E1-E4+ Advector, but not E1-E4- Advector, resulted in downregulation of expression of chemocytokines, including interleukin-8, MCP-1, RANTES, and GM-CSF. Nonetheless, a large number of leukocytes migrated through ECs infected with E1-E4+, but not those infected with E1-E4-, in response to exogenous chemokines. These results demonstrate that infection of ECs with E1-E4+ Advectors, but not E1-E4- Advectors, may directly augment inflammatory responses by upregulating expression of adhesion molecules and enhancing migration through Advector-infected ECs and suggest that E1-E4- Advectors may be a better choice for gene-transfer strategies directed to the ECs.

Original languageEnglish
Pages (from-to)903-910
Number of pages8
JournalCirculation Research
Volume88
Issue number9
DOIs
Publication statusPublished - 11 May 2001
Externally publishedYes

Fingerprint

Vascular Cell Adhesion Molecule-1
Intercellular Adhesion Molecule-1
Chemokines
Adenoviridae
Endothelium
Leukocytes
Infection
Genes
Up-Regulation
Chemokine CCL5
Umbilical Veins
P-Selectin
E-Selectin
Cell Adhesion Molecules
HLA-DR Antigens
Granulocyte-Macrophage Colony-Stimulating Factor
Interleukin-8
Transgenes
Leukocyte Count
Blood Vessels

Keywords

  • Adhesion molecules
  • E4 adenoviral vectors
  • Endothelial activation
  • Leukocyte adhesion

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Infection of endothelium with E1-E4+, but not E1-E4-, adenovirus gene transfer vectors enhances leukocyte adhesion and migration by modulation of ICAM-1, VCAM-1, CD34, and chemokine expression. / Rafii, Shahin; Dias, Sergio; Meeus, Sarah; Hattori, Koichi; Ramachandran, Ramalingam; Feuerback, Fred; Worgall, Stefan; Hackett, Neil R.; Crystal, Ronald.

In: Circulation Research, Vol. 88, No. 9, 11.05.2001, p. 903-910.

Research output: Contribution to journalArticle

Rafii, Shahin ; Dias, Sergio ; Meeus, Sarah ; Hattori, Koichi ; Ramachandran, Ramalingam ; Feuerback, Fred ; Worgall, Stefan ; Hackett, Neil R. ; Crystal, Ronald. / Infection of endothelium with E1-E4+, but not E1-E4-, adenovirus gene transfer vectors enhances leukocyte adhesion and migration by modulation of ICAM-1, VCAM-1, CD34, and chemokine expression. In: Circulation Research. 2001 ; Vol. 88, No. 9. pp. 903-910.
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abstract = "Intravascular introduction of replication-deficient adenoviral vectors (Advectors) provides an ideal model of delivery of transgenes for the treatment of various vascular abnormalities. On the basis of the knowledge that Advectors can induce inflammatory responses after intravascular administration, we speculated that cellular activation by Advector infection could directly modulate the endothelial cell (EC) adhesion molecule/chemokine expression repertoire. Infection of human umbilical vein ECs or bone marrow microvascular ECs with an E1-E4+ Advector resulted in the upregulation of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and CD34, but not E-selectin, P-selectin, CD36, CD13, CD44, HLA-DR or PECAM. Upregulation of ICAM-1, VCAM-1, and CD34 was apparent 12 hours after infection and persisted for weeks after infection. Selective induction of adhesion molecules was mediated by the presence of the E4 gene in the Advector, because infection of ECs with an E1-E4- Advector had no effect on adhesion molecule expression. ECs infected with E1-E4+ Advector, but not those infected with E1-E4- Advector, supported the adhesion of leukocytes. Monoclonal antibodies to ICAM-1 and VCAM-1 inhibited adhesion of leukocytes to E1-E4+-infected ECs. Infection of the ECs with E1-E4+ Advector, but not E1-E4- Advector, resulted in downregulation of expression of chemocytokines, including interleukin-8, MCP-1, RANTES, and GM-CSF. Nonetheless, a large number of leukocytes migrated through ECs infected with E1-E4+, but not those infected with E1-E4-, in response to exogenous chemokines. These results demonstrate that infection of ECs with E1-E4+ Advectors, but not E1-E4- Advectors, may directly augment inflammatory responses by upregulating expression of adhesion molecules and enhancing migration through Advector-infected ECs and suggest that E1-E4- Advectors may be a better choice for gene-transfer strategies directed to the ECs.",
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AU - Dias, Sergio

AU - Meeus, Sarah

AU - Hattori, Koichi

AU - Ramachandran, Ramalingam

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AU - Worgall, Stefan

AU - Hackett, Neil R.

AU - Crystal, Ronald

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