Upregulated expression and function of integrin adhesive receptors in systemic lupus erythematosus patients with vasculitis

Tsutomu Takeuchi, Kouichi Amano, Hiromi Sekine, Jun Koide, Tohru Abe

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

Upregulation of integrin adhesive receptors has been implicated in various pathological conditions. We examined expression and function of integrin adhesive receptors on peripheral blood lymphocytes from patients with systemic lupus erythematosus (SLE), particularly those with the complication of vasculitis, and found that VLA-4 and LFA-1 expression was increased in SLE patients with vasculitis, while LFA-1 but not VLA-4 expression was increased in those without vasculitis. These results suggested a role of VLA-4 in the pathogenesis of vasculitis in SLE. Functional studies further demonstrated that adhesion to cytokine-activated human umbilical cord vein endothelial cells and to the CS-1 alternatively spliced domain of fibronectin was significantly increased in SLE patients with vasculitis. Analysis of the functional epitopes on the α4 chain demonstrated that antigen densities of all the functional epitopes were increased in those with vasculitis, indicating that the increased expression of VLA-4 resulted from the increased number of VLA-4 molecules, and was not secondary to an increase in one particular functional epitope. Immunoprecipitation studies further support these results. Interestingly, high molecular weight bands associated with VLA-4 were observed in about half of the SLE patients with vasculitis. These results introduce a possibility that upregulation of integrin adhesive receptors has a potential role in the pathogenesis of vasculitis in SLE.

Original languageEnglish
Pages (from-to)3008-3016
Number of pages9
JournalJournal of Clinical Investigation
Volume92
Issue number6
Publication statusPublished - 1993 Dec
Externally publishedYes

Fingerprint

Integrin alpha4beta1
Vasculitis
Integrins
Systemic Lupus Erythematosus
Adhesives
Epitopes
Lymphocyte Function-Associated Antigen-1
Up-Regulation
Umbilical Cord
Human Umbilical Vein Endothelial Cells
Fibronectins
Immunoprecipitation
Molecular Weight
Lymphocytes
Cytokines
Antigens

Keywords

  • Integrins
  • LFA-1
  • Systemic lupus erythematosus
  • Vasculitis
  • VLA-4

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Upregulated expression and function of integrin adhesive receptors in systemic lupus erythematosus patients with vasculitis. / Takeuchi, Tsutomu; Amano, Kouichi; Sekine, Hiromi; Koide, Jun; Abe, Tohru.

In: Journal of Clinical Investigation, Vol. 92, No. 6, 12.1993, p. 3008-3016.

Research output: Contribution to journalArticle

@article{1e3e9fc8dbc14dfab5cd2267e2edfe36,
title = "Upregulated expression and function of integrin adhesive receptors in systemic lupus erythematosus patients with vasculitis",
abstract = "Upregulation of integrin adhesive receptors has been implicated in various pathological conditions. We examined expression and function of integrin adhesive receptors on peripheral blood lymphocytes from patients with systemic lupus erythematosus (SLE), particularly those with the complication of vasculitis, and found that VLA-4 and LFA-1 expression was increased in SLE patients with vasculitis, while LFA-1 but not VLA-4 expression was increased in those without vasculitis. These results suggested a role of VLA-4 in the pathogenesis of vasculitis in SLE. Functional studies further demonstrated that adhesion to cytokine-activated human umbilical cord vein endothelial cells and to the CS-1 alternatively spliced domain of fibronectin was significantly increased in SLE patients with vasculitis. Analysis of the functional epitopes on the α4 chain demonstrated that antigen densities of all the functional epitopes were increased in those with vasculitis, indicating that the increased expression of VLA-4 resulted from the increased number of VLA-4 molecules, and was not secondary to an increase in one particular functional epitope. Immunoprecipitation studies further support these results. Interestingly, high molecular weight bands associated with VLA-4 were observed in about half of the SLE patients with vasculitis. These results introduce a possibility that upregulation of integrin adhesive receptors has a potential role in the pathogenesis of vasculitis in SLE.",
keywords = "Integrins, LFA-1, Systemic lupus erythematosus, Vasculitis, VLA-4",
author = "Tsutomu Takeuchi and Kouichi Amano and Hiromi Sekine and Jun Koide and Tohru Abe",
year = "1993",
month = "12",
language = "English",
volume = "92",
pages = "3008--3016",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "6",

}

TY - JOUR

T1 - Upregulated expression and function of integrin adhesive receptors in systemic lupus erythematosus patients with vasculitis

AU - Takeuchi, Tsutomu

AU - Amano, Kouichi

AU - Sekine, Hiromi

AU - Koide, Jun

AU - Abe, Tohru

PY - 1993/12

Y1 - 1993/12

N2 - Upregulation of integrin adhesive receptors has been implicated in various pathological conditions. We examined expression and function of integrin adhesive receptors on peripheral blood lymphocytes from patients with systemic lupus erythematosus (SLE), particularly those with the complication of vasculitis, and found that VLA-4 and LFA-1 expression was increased in SLE patients with vasculitis, while LFA-1 but not VLA-4 expression was increased in those without vasculitis. These results suggested a role of VLA-4 in the pathogenesis of vasculitis in SLE. Functional studies further demonstrated that adhesion to cytokine-activated human umbilical cord vein endothelial cells and to the CS-1 alternatively spliced domain of fibronectin was significantly increased in SLE patients with vasculitis. Analysis of the functional epitopes on the α4 chain demonstrated that antigen densities of all the functional epitopes were increased in those with vasculitis, indicating that the increased expression of VLA-4 resulted from the increased number of VLA-4 molecules, and was not secondary to an increase in one particular functional epitope. Immunoprecipitation studies further support these results. Interestingly, high molecular weight bands associated with VLA-4 were observed in about half of the SLE patients with vasculitis. These results introduce a possibility that upregulation of integrin adhesive receptors has a potential role in the pathogenesis of vasculitis in SLE.

AB - Upregulation of integrin adhesive receptors has been implicated in various pathological conditions. We examined expression and function of integrin adhesive receptors on peripheral blood lymphocytes from patients with systemic lupus erythematosus (SLE), particularly those with the complication of vasculitis, and found that VLA-4 and LFA-1 expression was increased in SLE patients with vasculitis, while LFA-1 but not VLA-4 expression was increased in those without vasculitis. These results suggested a role of VLA-4 in the pathogenesis of vasculitis in SLE. Functional studies further demonstrated that adhesion to cytokine-activated human umbilical cord vein endothelial cells and to the CS-1 alternatively spliced domain of fibronectin was significantly increased in SLE patients with vasculitis. Analysis of the functional epitopes on the α4 chain demonstrated that antigen densities of all the functional epitopes were increased in those with vasculitis, indicating that the increased expression of VLA-4 resulted from the increased number of VLA-4 molecules, and was not secondary to an increase in one particular functional epitope. Immunoprecipitation studies further support these results. Interestingly, high molecular weight bands associated with VLA-4 were observed in about half of the SLE patients with vasculitis. These results introduce a possibility that upregulation of integrin adhesive receptors has a potential role in the pathogenesis of vasculitis in SLE.

KW - Integrins

KW - LFA-1

KW - Systemic lupus erythematosus

KW - Vasculitis

KW - VLA-4

UR - http://www.scopus.com/inward/record.url?scp=0027144105&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027144105&partnerID=8YFLogxK

M3 - Article

VL - 92

SP - 3008

EP - 3016

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 6

ER -