Home LiteratureArticle Details
PMID: 7964481 Published · ppublish English Journal Article

Expression of the chemokine N51/KC in the thymus and epidermis of transgenic mice results in marked infiltration of a single class of inflammatory cells.

The Journal of experimental medicine ·Vol. 180 ·No. 6 ·1994-12-01 ·Pages 2039-48

Lira SA, Zalamea P, Heinrich JN, Fuentes ME, Carrasco D, Lewin AC, Barton DS, Durham S, Bravo R

Abstract

Transgenic mice expressing the chemokine N51/KC in thymus, skin, and tongue showed a marked infiltration of a single class of inflammatory cells (neutrophils) in the sites of transgene expression. In the thymus, neutrophils were most numerous in the cortex and juxta-medullary regions, often forming aggregates or clusters. A similar, but less intense, neutrophilic infiltrate occurred in close proximity to the epidermal basal layer of the tongue and skin. No morphologic evidence of injury was observed in the thymus, skin, or tongue of these transgenic mice, indicating that N51/KC expression induces recruitment but not inflammatory activation of neutrophils. The lack of activation in the thymus resulted in a large senescent neutrophilic population that was phagocytosed by thymic macrophages and epithelial-reticular cells. These results indicate that N51/KC is a neutrophil chemoattractant in vivo and establish these transgenic mice as effective models to study the phenomena of recruitment and clearance of neutrophils, events that are critical for the initiation and resolution of the inflammatory response.

MeSH Terms
Aging/metabolism Animals Base Sequence Chemokine CXCL1 Chemokines, CXC Chemotactic Factors/biosynthesis Gene Expression Growth Hormone/biosynthesis,genetics Growth Substances/biosynthesis Humans Inflammation/physiopathology Intercellular Signaling Peptides and Proteins Mice Mice, Inbred C57BL Mice, Inbred DBA Mice, Transgenic Microscopy, Electron Molecular Sequence Data Neutrophils/metabolism,physiology Oligodeoxyribonucleotides Skin/metabolism Thymus Gland/growth & development,metabolism,ultrastructure Tongue/metabolism
Chemicals
CXCL1 protein, human Chemokine CXCL1 Chemokines, CXC Chemotactic Factors Cxcl1 protein, mouse Growth Substances Intercellular Signaling Peptides and Proteins Oligodeoxyribonucleotides Growth Hormone
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Lira S A
Department of Molecular Biology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543.
Zalamea P
Heinrich J N
Fuentes M E
Carrasco D
Lewin A C
Barton D S
Durham S
Bravo R
References (42)
42 references, click to expand
  1. Targeting expression of keratinocyte growth factor to keratinocytes elicits striking changes in epithelial differentiation in transgenic mice.
    EMBO J. 1993 Mar;12(3):973-86 PMID: 7681397
  2. Histologic fixatives suitable for diagnostic light and electron microscopy.
    Arch Pathol Lab Med. 1976 Aug;100(8):405-14 PMID: 60092
  3. Expression of a tumor necrosis factor alpha transgene in murine pancreatic beta cells results in severe and permanent insulitis without evolution towards diabetes.
    J Exp Med. 1992 Dec 1;176(6):1719-31 PMID: 1460428
  4. Transgenic mice expressing human tumour necrosis factor: a predictive genetic model of arthritis.
    EMBO J. 1991 Dec;10(13):4025-31 PMID: 1721867
  5. An upstream region of the mouse ZP3 gene directs expression of firefly luciferase specifically to growing oocytes in transgenic mice.
    Proc Natl Acad Sci U S A. 1990 Sep;87(18):7215-9 PMID: 2402504
  6. Origin of crystalloid inclusions in macrophages II: evidence for derivation from eosinophil granulocyte breakdown.
    Br J Exp Pathol. 1981 Dec;62(6):662-8 PMID: 6275877
  7. The platelet-derived growth factor-inducible KC gene encodes a secretory protein related to platelet alpha-granule proteins.
    J Biol Chem. 1989 Mar 5;264(7):4133-7 PMID: 2917992
  8. Molecular cloning of gene sequences regulated by platelet-derived growth factor.
    Cell. 1983 Jul;33(3):939-47 PMID: 6872001
  9. Inflammation but not autoimmunity occurs in transgenic mice expressing constitutive levels of interleukin-2 in islet beta cells.
    Eur J Immunol. 1992 May;22(5):1115-21 PMID: 1577058
  10. Cloning and sequence of a secretory protein induced by growth factors in mouse fibroblasts.
    Exp Cell Res. 1989 Jan;180(1):266-75 PMID: 2909392
  11. Endothelial-leukocyte adhesion molecules.
    Annu Rev Immunol. 1993;11:767-804 PMID: 8476577
  12. Endothelial cell binding of NAP-1/IL-8: role in neutrophil emigration.
    Immunol Today. 1992 Aug;13(8):291-4 PMID: 1510812
  13. Factors influencing frequency production of transgenic mice.
    Methods Enzymol. 1993;225:771-81 PMID: 8231885
  14. The neutrophil chemoattractant produced by the rat kidney epithelioid cell line NRK-52E is a protein related to the KC/gro protein.
    J Biol Chem. 1989 Nov 25;264(33):19559-63 PMID: 2684956
  15. Chemokines: combinatorial mediators of inflammation?
    Curr Biol. 1993 Jun 1;3(6):366-8 PMID: 15335733
  16. Expression of macrophage inflammatory protein-2 and KC mRNA in pulmonary inflammation.
    Am J Pathol. 1992 Oct;141(4):981-8 PMID: 1415488
  17. Cachexia and graft-vs.-host-disease-type skin changes in keratin promoter-driven TNF alpha transgenic mice.
    Genes Dev. 1992 Aug;6(8):1444-56 PMID: 1379563
  18. The product of a novel growth factor-activated gene, fic, is a biologically active "C-C"-type cytokine.
    Mol Cell Biol. 1993 Apr;13(4):2020-30 PMID: 8455595
  19. Resolution of acute inflammation and the role of apoptosis in the tissue fate of granulocytes.
    Clin Sci (Lond). 1992 Dec;83(6):639-48 PMID: 1336433
  20. Transgenic mice expressing a B cell growth and differentiation factor gene (interleukin 5) develop eosinophilia and autoantibody production.
    J Exp Med. 1991 Feb 1;173(2):429-37 PMID: 1988543
  21. Macrophage phagocytosis of aging neutrophils in inflammation. Programmed cell death in the neutrophil leads to its recognition by macrophages.
    J Clin Invest. 1989 Mar;83(3):865-75 PMID: 2921324
  22. Glomerular mesangial cells and inflammatory macrophages ingest neutrophils undergoing apoptosis.
    Kidney Int. 1992 Oct;42(4):924-36 PMID: 1333549
  23. Expression of relB transcripts during lymphoid organ development: specific expression in dendritic antigen-presenting cells.
    Development. 1993 Aug;118(4):1221-31 PMID: 8269849
  24. Lymphocyte infiltration into cerebellum in transgenic mice carrying human IL-2 gene.
    Int Immunol. 1989;1(2):214-8 PMID: 2487686
  25. Insulitis in transgenic mice expressing tumor necrosis factor beta (lymphotoxin) in the pancreas.
    Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10036-40 PMID: 1279667
  26. IL-4 induces allergic-like inflammatory disease and alters T cell development in transgenic mice.
    Cell. 1990 Aug 10;62(3):457-67 PMID: 2116236
  27. Properties of the novel proinflammatory supergene "intercrine" cytokine family.
    Annu Rev Immunol. 1991;9:617-48 PMID: 1910690
  28. Subversion of the immune system by pathogens.
    Cell. 1994 Jan 28;76(2):323-32 PMID: 8293466
  29. Biology and biochemistry of the chemokines: a family of chemotactic and inflammatory cytokines.
    Crit Rev Immunol. 1992;12(1-2):17-46 PMID: 1418604
  30. Crystalloid material in cells of the murine mononuclear phagocyte system.
    J Anat. 1988 Apr;157:217-28 PMID: 2848792
  31. Polymorphic expression of a neutrophil differentiation antigen revealed by monoclonal antibody 7/4.
    Immunogenetics. 1983;18(3):229-39 PMID: 6618532
  32. Transgenic tumor necrosis factor (TNF)-alpha production in pancreatic islets leads to insulitis, not diabetes. Distinct patterns of inflammation in TNF-alpha and TNF-beta transgenic mice.
    J Immunol. 1993 May 1;150(9):4136-50 PMID: 7682590
  33. Leukocyte-endothelial cell recognition: three (or more) steps to specificity and diversity.
    Cell. 1991 Dec 20;67(6):1033-6 PMID: 1760836
  34. Eosinophilia in transgenic mice expressing interleukin 5.
    J Exp Med. 1990 Nov 1;172(5):1425-31 PMID: 2230651
  35. Apoptosis: mechanisms and roles in pathology.
    Int Rev Exp Pathol. 1991;32:223-54 PMID: 1677933
  36. Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm.
    Cell. 1994 Jan 28;76(2):301-14 PMID: 7507411
  37. The effect of LPS on expression of the early "competence" genes JE and KC in murine peritoneal macrophages.
    J Immunol. 1987 Jun 1;138(11):3891-6 PMID: 3108379
  38. Leukocyte extravasation into the pancreatic tissue in transgenic mice expressing interleukin 10 in the islets of Langerhans.
    J Exp Med. 1993 Jul 1;178(1):175-85 PMID: 8100268
  39. Lipopolysaccharide-induced expression of the competence gene KC in vascular endothelial cells is mediated through protein kinase C.
    J Cell Physiol. 1989 Jul;140(1):44-51 PMID: 2472419
  40. Biological activity of the growth factor-induced cytokine N51: structure-function analysis using N51/Interleukin-8 chimeric molecules.
    Mol Cell Biol. 1994 May;14(5):2849-61 PMID: 8164648
  41. Cytoplasmic dot hybridization. Simple analysis of relative mRNA levels in multiple small cell or tissue samples.
    J Biol Chem. 1982 Aug 10;257(15):8569-72 PMID: 7096324
  42. Regulation of T cell receptor signaling by a src family protein-tyrosine kinase (p59fyn).
    Cell. 1991 Apr 19;65(2):281-91 PMID: 2015626
Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
Published
1994-12-01
Pages
2039-48
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2191760
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]