Effect of antibody against integrin α4 on bleomycin-induced pulmonary fibrosis in mice

Qingjian Wang, Yingjin Wang, Dallas M. Hyde, Philip J. Gotwals, Roy R. Lobb, Sarah T. Ryan, Shri N. Giri

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Integrins are a family of transmembrane glycoproteins that can interact with components of the extracellular matrix. The α4β1 and α4β7 integrins are heterodimeric leukocyte cell surface molecules critical to their cell and matrix adhesive interactions. Evidence for a central role for the α4 integrins in leukocyte pathophysiology in the lung is well documented. In this study, we tested the hypothesis that neutralizing antibody for integrin α4 (PS2) may reduce bleomycin (BL)-induced lung fibrosis in vivo. Male C57BL/6 mice were injected intratracheally with saline (SA) or BL (0.08 U/mouse) followed by intraperitoneal injection of SA, isotype control antibody (1E6), or PS2 (100 μg) three times a week. Twenty-one days after the intratracheal instillation, mice were killed for bronchoalveolar lavage (BAL), biochemical, histopathological, and immunohistological analyses. Treatment with PS2 significantly reduced BL-induced increases in lung lipid peroxidation and hydroxyproline content. Lung histopathology also showed reduced fibrotic lesions in the BL-treated lungs by treatment with PS2. BL-treated mouse lungs also showed induction of cells with the myofibroblast phenotype, as indicated by the increased expression of α-smooth muscle actin (αSMA), whereas treatment with PS2 minimized the BL-induced αSMA expression. Furthermore, treatment with PS2 reduced the BL-induced increase in the BAL total cell number, and attenuated the BL-induced increase in the BAL protein level. It is concluded that integrin α4 may play an important role in BL-induced pulmonary fibrosis, and the use of anti-α4 antibody offers therapeutic antifibrotic potential in vivo. (C) 2000 Elsevier Science Inc.

Original languageEnglish (US)
Pages (from-to)1949-1958
Number of pages10
JournalBiochemical Pharmacology
Volume60
Issue number12
DOIs
StatePublished - Dec 15 2000

Fingerprint

Pulmonary Fibrosis
Bleomycin
Integrins
Antibodies
Lung
Bronchoalveolar Lavage
Smooth Muscle
Muscle
Actins
Leukocytes
Therapeutics
Myofibroblasts
Hydroxyproline
Neutralizing Antibodies
Intraperitoneal Injections
Inbred C57BL Mouse
Adhesives
Lipid Peroxidation
Extracellular Matrix
Anti-Idiotypic Antibodies

Keywords

  • Collagen
  • Integrin
  • Lung fibrosis
  • Mouse
  • Myofibroblast

ASJC Scopus subject areas

  • Pharmacology

Cite this

Wang, Q., Wang, Y., Hyde, D. M., Gotwals, P. J., Lobb, R. R., Ryan, S. T., & Giri, S. N. (2000). Effect of antibody against integrin α4 on bleomycin-induced pulmonary fibrosis in mice. Biochemical Pharmacology, 60(12), 1949-1958. https://doi.org/10.1016/S0006-2952(00)00491-3

Effect of antibody against integrin α4 on bleomycin-induced pulmonary fibrosis in mice. / Wang, Qingjian; Wang, Yingjin; Hyde, Dallas M.; Gotwals, Philip J.; Lobb, Roy R.; Ryan, Sarah T.; Giri, Shri N.

In: Biochemical Pharmacology, Vol. 60, No. 12, 15.12.2000, p. 1949-1958.

Research output: Contribution to journalArticle

Wang, Q, Wang, Y, Hyde, DM, Gotwals, PJ, Lobb, RR, Ryan, ST & Giri, SN 2000, 'Effect of antibody against integrin α4 on bleomycin-induced pulmonary fibrosis in mice', Biochemical Pharmacology, vol. 60, no. 12, pp. 1949-1958. https://doi.org/10.1016/S0006-2952(00)00491-3
Wang, Qingjian ; Wang, Yingjin ; Hyde, Dallas M. ; Gotwals, Philip J. ; Lobb, Roy R. ; Ryan, Sarah T. ; Giri, Shri N. / Effect of antibody against integrin α4 on bleomycin-induced pulmonary fibrosis in mice. In: Biochemical Pharmacology. 2000 ; Vol. 60, No. 12. pp. 1949-1958.
@article{3df70a08495f428e9ab4b1a4fecb55c3,
title = "Effect of antibody against integrin α4 on bleomycin-induced pulmonary fibrosis in mice",
abstract = "Integrins are a family of transmembrane glycoproteins that can interact with components of the extracellular matrix. The α4β1 and α4β7 integrins are heterodimeric leukocyte cell surface molecules critical to their cell and matrix adhesive interactions. Evidence for a central role for the α4 integrins in leukocyte pathophysiology in the lung is well documented. In this study, we tested the hypothesis that neutralizing antibody for integrin α4 (PS2) may reduce bleomycin (BL)-induced lung fibrosis in vivo. Male C57BL/6 mice were injected intratracheally with saline (SA) or BL (0.08 U/mouse) followed by intraperitoneal injection of SA, isotype control antibody (1E6), or PS2 (100 μg) three times a week. Twenty-one days after the intratracheal instillation, mice were killed for bronchoalveolar lavage (BAL), biochemical, histopathological, and immunohistological analyses. Treatment with PS2 significantly reduced BL-induced increases in lung lipid peroxidation and hydroxyproline content. Lung histopathology also showed reduced fibrotic lesions in the BL-treated lungs by treatment with PS2. BL-treated mouse lungs also showed induction of cells with the myofibroblast phenotype, as indicated by the increased expression of α-smooth muscle actin (αSMA), whereas treatment with PS2 minimized the BL-induced αSMA expression. Furthermore, treatment with PS2 reduced the BL-induced increase in the BAL total cell number, and attenuated the BL-induced increase in the BAL protein level. It is concluded that integrin α4 may play an important role in BL-induced pulmonary fibrosis, and the use of anti-α4 antibody offers therapeutic antifibrotic potential in vivo. (C) 2000 Elsevier Science Inc.",
keywords = "Collagen, Integrin, Lung fibrosis, Mouse, Myofibroblast",
author = "Qingjian Wang and Yingjin Wang and Hyde, {Dallas M.} and Gotwals, {Philip J.} and Lobb, {Roy R.} and Ryan, {Sarah T.} and Giri, {Shri N.}",
year = "2000",
month = "12",
day = "15",
doi = "10.1016/S0006-2952(00)00491-3",
language = "English (US)",
volume = "60",
pages = "1949--1958",
journal = "Biochemical Pharmacology",
issn = "0006-2952",
publisher = "Elsevier Inc.",
number = "12",

}

TY - JOUR

T1 - Effect of antibody against integrin α4 on bleomycin-induced pulmonary fibrosis in mice

AU - Wang, Qingjian

AU - Wang, Yingjin

AU - Hyde, Dallas M.

AU - Gotwals, Philip J.

AU - Lobb, Roy R.

AU - Ryan, Sarah T.

AU - Giri, Shri N.

PY - 2000/12/15

Y1 - 2000/12/15

N2 - Integrins are a family of transmembrane glycoproteins that can interact with components of the extracellular matrix. The α4β1 and α4β7 integrins are heterodimeric leukocyte cell surface molecules critical to their cell and matrix adhesive interactions. Evidence for a central role for the α4 integrins in leukocyte pathophysiology in the lung is well documented. In this study, we tested the hypothesis that neutralizing antibody for integrin α4 (PS2) may reduce bleomycin (BL)-induced lung fibrosis in vivo. Male C57BL/6 mice were injected intratracheally with saline (SA) or BL (0.08 U/mouse) followed by intraperitoneal injection of SA, isotype control antibody (1E6), or PS2 (100 μg) three times a week. Twenty-one days after the intratracheal instillation, mice were killed for bronchoalveolar lavage (BAL), biochemical, histopathological, and immunohistological analyses. Treatment with PS2 significantly reduced BL-induced increases in lung lipid peroxidation and hydroxyproline content. Lung histopathology also showed reduced fibrotic lesions in the BL-treated lungs by treatment with PS2. BL-treated mouse lungs also showed induction of cells with the myofibroblast phenotype, as indicated by the increased expression of α-smooth muscle actin (αSMA), whereas treatment with PS2 minimized the BL-induced αSMA expression. Furthermore, treatment with PS2 reduced the BL-induced increase in the BAL total cell number, and attenuated the BL-induced increase in the BAL protein level. It is concluded that integrin α4 may play an important role in BL-induced pulmonary fibrosis, and the use of anti-α4 antibody offers therapeutic antifibrotic potential in vivo. (C) 2000 Elsevier Science Inc.

AB - Integrins are a family of transmembrane glycoproteins that can interact with components of the extracellular matrix. The α4β1 and α4β7 integrins are heterodimeric leukocyte cell surface molecules critical to their cell and matrix adhesive interactions. Evidence for a central role for the α4 integrins in leukocyte pathophysiology in the lung is well documented. In this study, we tested the hypothesis that neutralizing antibody for integrin α4 (PS2) may reduce bleomycin (BL)-induced lung fibrosis in vivo. Male C57BL/6 mice were injected intratracheally with saline (SA) or BL (0.08 U/mouse) followed by intraperitoneal injection of SA, isotype control antibody (1E6), or PS2 (100 μg) three times a week. Twenty-one days after the intratracheal instillation, mice were killed for bronchoalveolar lavage (BAL), biochemical, histopathological, and immunohistological analyses. Treatment with PS2 significantly reduced BL-induced increases in lung lipid peroxidation and hydroxyproline content. Lung histopathology also showed reduced fibrotic lesions in the BL-treated lungs by treatment with PS2. BL-treated mouse lungs also showed induction of cells with the myofibroblast phenotype, as indicated by the increased expression of α-smooth muscle actin (αSMA), whereas treatment with PS2 minimized the BL-induced αSMA expression. Furthermore, treatment with PS2 reduced the BL-induced increase in the BAL total cell number, and attenuated the BL-induced increase in the BAL protein level. It is concluded that integrin α4 may play an important role in BL-induced pulmonary fibrosis, and the use of anti-α4 antibody offers therapeutic antifibrotic potential in vivo. (C) 2000 Elsevier Science Inc.

KW - Collagen

KW - Integrin

KW - Lung fibrosis

KW - Mouse

KW - Myofibroblast

UR - http://www.scopus.com/inward/record.url?scp=0034672441&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034672441&partnerID=8YFLogxK

U2 - 10.1016/S0006-2952(00)00491-3

DO - 10.1016/S0006-2952(00)00491-3

M3 - Article

VL - 60

SP - 1949

EP - 1958

JO - Biochemical Pharmacology

JF - Biochemical Pharmacology

SN - 0006-2952

IS - 12

ER -