Eosinophilia in transgenic mice expressing interleukin 5

Lindsay A. Dent, Malcolm Strath, Andrew L. Mellor, Colin J. Sanderson

Research output: Contribution to journalArticle

466 Citations (Scopus)

Abstract

Experiments in vitro suggest that although interleukin 5 (IL5) stimulates the late stages ofeosinophil differentiation, other cytokines are required for the generation of eosinophil progenitor cells. In this study transgenic mice constitutively expressing the IL-5 gene were established using a genomic fragment of the 11,5 gene coupled to the dominant control region from the gene encoding human CD2. Four independent eosinophilic transgenic lines have thus far been established, two ofwhich with 8 and 49 transgene copies, are described in detail. These mice appeared macroscopically normal apart from splenomegaly. Eosinophils were at least 65- and 265-fold higher in blood from transgenics, relative to normal littermates, and approximately two- or sevenfold more numerous relative to blood from mice infected with the helminth Mesocestoides corti. Much more modest increases in blood neutrophil, lymphocyte, and monocyte numbers were noted in transgenics, relative to normal littermates (less than threefold). Thus IL-5 in vivo is relatively specific for the eosinophil lineage. Large numbers ofeosinophils were present in spleen, bone marrow, and peritoneal exudate, and were highest in the line with the greatest transgene copy number. Eosinophilia was also noted in histological sections of transgenic lungs, Peyer’s patches, mesenteric lymph nodes, and gut lamina propria but not in other tissues examined. 11,5 was detected in the sera of transgenics at levels comparable to those seen in sera from parasite-infected animals. IL3 and granulocyte/macrophage colony-stimulating factor (GM-CSF) were not found. 11,5 mRNA was detected in transgenic thymus, Peyer’s patches, and superficial lymph nodes, but not in heart, liver, brain, or skeletal muscle or in any tissues from nontransgenics. Bone marrow from transgenic mice was rich in 11,5-dependent eosinophil precursors. These data indicate that induction of the IL-5 gene is sufficient for production ofeosinophilia, and that IL-5 can induce the full pathway of eosinophil differentiation. IL-5 may therefore not be restricted in action to the later stages of eosinophil differentiation, as suggested by earlier in vitro studies.

Original languageEnglish (US)
Pages (from-to)1425-1431
Number of pages7
JournalJournal of Experimental Medicine
Volume172
Issue number5
DOIs
StatePublished - Nov 1 1990

Fingerprint

Interleukin-5
Eosinophilia
Eosinophils
Transgenic Mice
Peyer's Patches
Transgenes
Genes
Mesocestoides
Lymph Nodes
Bone Marrow
Helminths
Splenomegaly
Lymphocyte Count
Exudates and Transudates
Granulocyte-Macrophage Colony-Stimulating Factor
Serum
Thymus Gland
Monocytes
Mucous Membrane
Parasites

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Dent, L. A., Strath, M., Mellor, A. L., & Sanderson, C. J. (1990). Eosinophilia in transgenic mice expressing interleukin 5. Journal of Experimental Medicine, 172(5), 1425-1431. https://doi.org/10.1084/jem.172.5.1425

Eosinophilia in transgenic mice expressing interleukin 5. / Dent, Lindsay A.; Strath, Malcolm; Mellor, Andrew L.; Sanderson, Colin J.

In: Journal of Experimental Medicine, Vol. 172, No. 5, 01.11.1990, p. 1425-1431.

Research output: Contribution to journalArticle

Dent, LA, Strath, M, Mellor, AL & Sanderson, CJ 1990, 'Eosinophilia in transgenic mice expressing interleukin 5', Journal of Experimental Medicine, vol. 172, no. 5, pp. 1425-1431. https://doi.org/10.1084/jem.172.5.1425
Dent, Lindsay A. ; Strath, Malcolm ; Mellor, Andrew L. ; Sanderson, Colin J. / Eosinophilia in transgenic mice expressing interleukin 5. In: Journal of Experimental Medicine. 1990 ; Vol. 172, No. 5. pp. 1425-1431.
@article{01aa08cf5b3e443e9d5b13fe553c83ec,
title = "Eosinophilia in transgenic mice expressing interleukin 5",
abstract = "Experiments in vitro suggest that although interleukin 5 (IL5) stimulates the late stages ofeosinophil differentiation, other cytokines are required for the generation of eosinophil progenitor cells. In this study transgenic mice constitutively expressing the IL-5 gene were established using a genomic fragment of the 11,5 gene coupled to the dominant control region from the gene encoding human CD2. Four independent eosinophilic transgenic lines have thus far been established, two ofwhich with 8 and 49 transgene copies, are described in detail. These mice appeared macroscopically normal apart from splenomegaly. Eosinophils were at least 65- and 265-fold higher in blood from transgenics, relative to normal littermates, and approximately two- or sevenfold more numerous relative to blood from mice infected with the helminth Mesocestoides corti. Much more modest increases in blood neutrophil, lymphocyte, and monocyte numbers were noted in transgenics, relative to normal littermates (less than threefold). Thus IL-5 in vivo is relatively specific for the eosinophil lineage. Large numbers ofeosinophils were present in spleen, bone marrow, and peritoneal exudate, and were highest in the line with the greatest transgene copy number. Eosinophilia was also noted in histological sections of transgenic lungs, Peyer’s patches, mesenteric lymph nodes, and gut lamina propria but not in other tissues examined. 11,5 was detected in the sera of transgenics at levels comparable to those seen in sera from parasite-infected animals. IL3 and granulocyte/macrophage colony-stimulating factor (GM-CSF) were not found. 11,5 mRNA was detected in transgenic thymus, Peyer’s patches, and superficial lymph nodes, but not in heart, liver, brain, or skeletal muscle or in any tissues from nontransgenics. Bone marrow from transgenic mice was rich in 11,5-dependent eosinophil precursors. These data indicate that induction of the IL-5 gene is sufficient for production ofeosinophilia, and that IL-5 can induce the full pathway of eosinophil differentiation. IL-5 may therefore not be restricted in action to the later stages of eosinophil differentiation, as suggested by earlier in vitro studies.",
author = "Dent, {Lindsay A.} and Malcolm Strath and Mellor, {Andrew L.} and Sanderson, {Colin J.}",
year = "1990",
month = "11",
day = "1",
doi = "10.1084/jem.172.5.1425",
language = "English (US)",
volume = "172",
pages = "1425--1431",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "5",

}

TY - JOUR

T1 - Eosinophilia in transgenic mice expressing interleukin 5

AU - Dent, Lindsay A.

AU - Strath, Malcolm

AU - Mellor, Andrew L.

AU - Sanderson, Colin J.

PY - 1990/11/1

Y1 - 1990/11/1

N2 - Experiments in vitro suggest that although interleukin 5 (IL5) stimulates the late stages ofeosinophil differentiation, other cytokines are required for the generation of eosinophil progenitor cells. In this study transgenic mice constitutively expressing the IL-5 gene were established using a genomic fragment of the 11,5 gene coupled to the dominant control region from the gene encoding human CD2. Four independent eosinophilic transgenic lines have thus far been established, two ofwhich with 8 and 49 transgene copies, are described in detail. These mice appeared macroscopically normal apart from splenomegaly. Eosinophils were at least 65- and 265-fold higher in blood from transgenics, relative to normal littermates, and approximately two- or sevenfold more numerous relative to blood from mice infected with the helminth Mesocestoides corti. Much more modest increases in blood neutrophil, lymphocyte, and monocyte numbers were noted in transgenics, relative to normal littermates (less than threefold). Thus IL-5 in vivo is relatively specific for the eosinophil lineage. Large numbers ofeosinophils were present in spleen, bone marrow, and peritoneal exudate, and were highest in the line with the greatest transgene copy number. Eosinophilia was also noted in histological sections of transgenic lungs, Peyer’s patches, mesenteric lymph nodes, and gut lamina propria but not in other tissues examined. 11,5 was detected in the sera of transgenics at levels comparable to those seen in sera from parasite-infected animals. IL3 and granulocyte/macrophage colony-stimulating factor (GM-CSF) were not found. 11,5 mRNA was detected in transgenic thymus, Peyer’s patches, and superficial lymph nodes, but not in heart, liver, brain, or skeletal muscle or in any tissues from nontransgenics. Bone marrow from transgenic mice was rich in 11,5-dependent eosinophil precursors. These data indicate that induction of the IL-5 gene is sufficient for production ofeosinophilia, and that IL-5 can induce the full pathway of eosinophil differentiation. IL-5 may therefore not be restricted in action to the later stages of eosinophil differentiation, as suggested by earlier in vitro studies.

AB - Experiments in vitro suggest that although interleukin 5 (IL5) stimulates the late stages ofeosinophil differentiation, other cytokines are required for the generation of eosinophil progenitor cells. In this study transgenic mice constitutively expressing the IL-5 gene were established using a genomic fragment of the 11,5 gene coupled to the dominant control region from the gene encoding human CD2. Four independent eosinophilic transgenic lines have thus far been established, two ofwhich with 8 and 49 transgene copies, are described in detail. These mice appeared macroscopically normal apart from splenomegaly. Eosinophils were at least 65- and 265-fold higher in blood from transgenics, relative to normal littermates, and approximately two- or sevenfold more numerous relative to blood from mice infected with the helminth Mesocestoides corti. Much more modest increases in blood neutrophil, lymphocyte, and monocyte numbers were noted in transgenics, relative to normal littermates (less than threefold). Thus IL-5 in vivo is relatively specific for the eosinophil lineage. Large numbers ofeosinophils were present in spleen, bone marrow, and peritoneal exudate, and were highest in the line with the greatest transgene copy number. Eosinophilia was also noted in histological sections of transgenic lungs, Peyer’s patches, mesenteric lymph nodes, and gut lamina propria but not in other tissues examined. 11,5 was detected in the sera of transgenics at levels comparable to those seen in sera from parasite-infected animals. IL3 and granulocyte/macrophage colony-stimulating factor (GM-CSF) were not found. 11,5 mRNA was detected in transgenic thymus, Peyer’s patches, and superficial lymph nodes, but not in heart, liver, brain, or skeletal muscle or in any tissues from nontransgenics. Bone marrow from transgenic mice was rich in 11,5-dependent eosinophil precursors. These data indicate that induction of the IL-5 gene is sufficient for production ofeosinophilia, and that IL-5 can induce the full pathway of eosinophil differentiation. IL-5 may therefore not be restricted in action to the later stages of eosinophil differentiation, as suggested by earlier in vitro studies.

UR - http://www.scopus.com/inward/record.url?scp=0025036906&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025036906&partnerID=8YFLogxK

U2 - 10.1084/jem.172.5.1425

DO - 10.1084/jem.172.5.1425

M3 - Article

C2 - 2230651

AN - SCOPUS:0025036906

VL - 172

SP - 1425

EP - 1431

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 5

ER -