Eosinophil recruitment to the lung in a murine model of allergic inflammation

The role of T cells, chemokines, and adhesion receptors

Jose Angel Gonzalo, Clare M. Lloyd, Leonor Kremer, Elizabeth Finger, C. Martinez-A., M. H. Siegelman, Myron Cybulsky, Jose Carlos Gutierrez-Ramos

Research output: Contribution to journalArticle

387 Citations (Scopus)

Abstract

Eosinophil accumulation is a distinctive feature of lung allergic inflammation. Here, we have used a mouse model of OVA (ovalbumin)-induced pulmonary eosinophilia to study the cellular and molecular mechanisms for this selective recruitment of eosinophils to the airways. In this model there was an early accumulation of infiltrating monocytes/macrophages in the lung during the OVA treatment, whereas the increase in infiltrating T-lymphocytes paralleled the accumulation of eosinophils. The kinetics of accumulation of these three leukocyte subtypes correlated with the levels of mRNA expression of the chemokines monocyte chemotactic peptide-1/JE, eotaxin, and RANTES (regulated upon activation in normal T cells expressed and secreted), suggesting their involvement in the recruitment of these leukocytes. Furthermore, blockade of eotaxin with specific antibodies in vivo reduced the accumulation of eosinophils in the lung in response to OVA by half. Mature CD4+ T-lymphocytes were absolutely required for OVA-induced eosinophil accumulation since lung eosinophilia was prevented in CD4+deficient mice. However, these cells were neither the main producers of the major eosinophilic chemokines eotaxin, RANTES, or MIP-1α, nor did they regulate the expression of these chemokines. Rather, the presence of CD4+ T cells was necessary for enhancement of VCAM-1 (vascular cell adhesion molecule-I) expression in the lung during allergic inflammation induced by the OVA treatment. In support of this, mice genetically deficient for VCAM-1 and intercellular adhesion molecule-1 failed to develop pulmonary eosinophilia. Selective eosinophilic recruitment during lung allergic inflammation results from a sequential accumulation of certain leukocyte types, particularly T cells, and relies on the presence of both eosinophilic chemoattractants and adhesion receptors.

Original languageEnglish (US)
Pages (from-to)2332-2345
Number of pages14
JournalJournal of Clinical Investigation
Volume98
Issue number10
StatePublished - Nov 15 1996

Fingerprint

Chemokine Receptors
T-Cell Antigen Receptor
Eosinophils
Cell Adhesion
Ovalbumin
Inflammation
T-Lymphocytes
Lung
Vascular Cell Adhesion Molecule-1
Chemokines
Pulmonary Eosinophilia
Leukocytes
Monocytes
Pneumonia
Chemokine CCL11
Formyl Peptide Receptor
Eosinophilia
Intercellular Adhesion Molecule-1
adhesion receptor
Macrophages

Keywords

  • chemotactic cytokines
  • integrins
  • leukocytes
  • lung eosinophilia
  • selectins

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Gonzalo, J. A., Lloyd, C. M., Kremer, L., Finger, E., Martinez-A., C., Siegelman, M. H., ... Gutierrez-Ramos, J. C. (1996). Eosinophil recruitment to the lung in a murine model of allergic inflammation: The role of T cells, chemokines, and adhesion receptors. Journal of Clinical Investigation, 98(10), 2332-2345.

Eosinophil recruitment to the lung in a murine model of allergic inflammation : The role of T cells, chemokines, and adhesion receptors. / Gonzalo, Jose Angel; Lloyd, Clare M.; Kremer, Leonor; Finger, Elizabeth; Martinez-A., C.; Siegelman, M. H.; Cybulsky, Myron; Gutierrez-Ramos, Jose Carlos.

In: Journal of Clinical Investigation, Vol. 98, No. 10, 15.11.1996, p. 2332-2345.

Research output: Contribution to journalArticle

Gonzalo, JA, Lloyd, CM, Kremer, L, Finger, E, Martinez-A., C, Siegelman, MH, Cybulsky, M & Gutierrez-Ramos, JC 1996, 'Eosinophil recruitment to the lung in a murine model of allergic inflammation: The role of T cells, chemokines, and adhesion receptors', Journal of Clinical Investigation, vol. 98, no. 10, pp. 2332-2345.
Gonzalo, Jose Angel ; Lloyd, Clare M. ; Kremer, Leonor ; Finger, Elizabeth ; Martinez-A., C. ; Siegelman, M. H. ; Cybulsky, Myron ; Gutierrez-Ramos, Jose Carlos. / Eosinophil recruitment to the lung in a murine model of allergic inflammation : The role of T cells, chemokines, and adhesion receptors. In: Journal of Clinical Investigation. 1996 ; Vol. 98, No. 10. pp. 2332-2345.
@article{ad79ae2029a542679865068d049ea084,
title = "Eosinophil recruitment to the lung in a murine model of allergic inflammation: The role of T cells, chemokines, and adhesion receptors",
abstract = "Eosinophil accumulation is a distinctive feature of lung allergic inflammation. Here, we have used a mouse model of OVA (ovalbumin)-induced pulmonary eosinophilia to study the cellular and molecular mechanisms for this selective recruitment of eosinophils to the airways. In this model there was an early accumulation of infiltrating monocytes/macrophages in the lung during the OVA treatment, whereas the increase in infiltrating T-lymphocytes paralleled the accumulation of eosinophils. The kinetics of accumulation of these three leukocyte subtypes correlated with the levels of mRNA expression of the chemokines monocyte chemotactic peptide-1/JE, eotaxin, and RANTES (regulated upon activation in normal T cells expressed and secreted), suggesting their involvement in the recruitment of these leukocytes. Furthermore, blockade of eotaxin with specific antibodies in vivo reduced the accumulation of eosinophils in the lung in response to OVA by half. Mature CD4+ T-lymphocytes were absolutely required for OVA-induced eosinophil accumulation since lung eosinophilia was prevented in CD4+deficient mice. However, these cells were neither the main producers of the major eosinophilic chemokines eotaxin, RANTES, or MIP-1α, nor did they regulate the expression of these chemokines. Rather, the presence of CD4+ T cells was necessary for enhancement of VCAM-1 (vascular cell adhesion molecule-I) expression in the lung during allergic inflammation induced by the OVA treatment. In support of this, mice genetically deficient for VCAM-1 and intercellular adhesion molecule-1 failed to develop pulmonary eosinophilia. Selective eosinophilic recruitment during lung allergic inflammation results from a sequential accumulation of certain leukocyte types, particularly T cells, and relies on the presence of both eosinophilic chemoattractants and adhesion receptors.",
keywords = "chemotactic cytokines, integrins, leukocytes, lung eosinophilia, selectins",
author = "Gonzalo, {Jose Angel} and Lloyd, {Clare M.} and Leonor Kremer and Elizabeth Finger and C. Martinez-A. and Siegelman, {M. H.} and Myron Cybulsky and Gutierrez-Ramos, {Jose Carlos}",
year = "1996",
month = "11",
day = "15",
language = "English (US)",
volume = "98",
pages = "2332--2345",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "10",

}

TY - JOUR

T1 - Eosinophil recruitment to the lung in a murine model of allergic inflammation

T2 - The role of T cells, chemokines, and adhesion receptors

AU - Gonzalo, Jose Angel

AU - Lloyd, Clare M.

AU - Kremer, Leonor

AU - Finger, Elizabeth

AU - Martinez-A., C.

AU - Siegelman, M. H.

AU - Cybulsky, Myron

AU - Gutierrez-Ramos, Jose Carlos

PY - 1996/11/15

Y1 - 1996/11/15

N2 - Eosinophil accumulation is a distinctive feature of lung allergic inflammation. Here, we have used a mouse model of OVA (ovalbumin)-induced pulmonary eosinophilia to study the cellular and molecular mechanisms for this selective recruitment of eosinophils to the airways. In this model there was an early accumulation of infiltrating monocytes/macrophages in the lung during the OVA treatment, whereas the increase in infiltrating T-lymphocytes paralleled the accumulation of eosinophils. The kinetics of accumulation of these three leukocyte subtypes correlated with the levels of mRNA expression of the chemokines monocyte chemotactic peptide-1/JE, eotaxin, and RANTES (regulated upon activation in normal T cells expressed and secreted), suggesting their involvement in the recruitment of these leukocytes. Furthermore, blockade of eotaxin with specific antibodies in vivo reduced the accumulation of eosinophils in the lung in response to OVA by half. Mature CD4+ T-lymphocytes were absolutely required for OVA-induced eosinophil accumulation since lung eosinophilia was prevented in CD4+deficient mice. However, these cells were neither the main producers of the major eosinophilic chemokines eotaxin, RANTES, or MIP-1α, nor did they regulate the expression of these chemokines. Rather, the presence of CD4+ T cells was necessary for enhancement of VCAM-1 (vascular cell adhesion molecule-I) expression in the lung during allergic inflammation induced by the OVA treatment. In support of this, mice genetically deficient for VCAM-1 and intercellular adhesion molecule-1 failed to develop pulmonary eosinophilia. Selective eosinophilic recruitment during lung allergic inflammation results from a sequential accumulation of certain leukocyte types, particularly T cells, and relies on the presence of both eosinophilic chemoattractants and adhesion receptors.

AB - Eosinophil accumulation is a distinctive feature of lung allergic inflammation. Here, we have used a mouse model of OVA (ovalbumin)-induced pulmonary eosinophilia to study the cellular and molecular mechanisms for this selective recruitment of eosinophils to the airways. In this model there was an early accumulation of infiltrating monocytes/macrophages in the lung during the OVA treatment, whereas the increase in infiltrating T-lymphocytes paralleled the accumulation of eosinophils. The kinetics of accumulation of these three leukocyte subtypes correlated with the levels of mRNA expression of the chemokines monocyte chemotactic peptide-1/JE, eotaxin, and RANTES (regulated upon activation in normal T cells expressed and secreted), suggesting their involvement in the recruitment of these leukocytes. Furthermore, blockade of eotaxin with specific antibodies in vivo reduced the accumulation of eosinophils in the lung in response to OVA by half. Mature CD4+ T-lymphocytes were absolutely required for OVA-induced eosinophil accumulation since lung eosinophilia was prevented in CD4+deficient mice. However, these cells were neither the main producers of the major eosinophilic chemokines eotaxin, RANTES, or MIP-1α, nor did they regulate the expression of these chemokines. Rather, the presence of CD4+ T cells was necessary for enhancement of VCAM-1 (vascular cell adhesion molecule-I) expression in the lung during allergic inflammation induced by the OVA treatment. In support of this, mice genetically deficient for VCAM-1 and intercellular adhesion molecule-1 failed to develop pulmonary eosinophilia. Selective eosinophilic recruitment during lung allergic inflammation results from a sequential accumulation of certain leukocyte types, particularly T cells, and relies on the presence of both eosinophilic chemoattractants and adhesion receptors.

KW - chemotactic cytokines

KW - integrins

KW - leukocytes

KW - lung eosinophilia

KW - selectins

UR - http://www.scopus.com/inward/record.url?scp=0029826642&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029826642&partnerID=8YFLogxK

M3 - Article

VL - 98

SP - 2332

EP - 2345

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 10

ER -