Constitutive expression of macrophage-inflammatory protein 2 (MIP-2) mRNA in bone marrow gives rise to peripheral neutrophils with preformed MIP-2 protein.

Abstract

Macrophage-inflammatory protein 2 (MIP-2) is a major CXC chemokine involved in the migration of polymorphonuclear neutrophils (PMNs) to sites of inflammation. Although cell culture experiments have identified different cell types that can produce MIP-2, the cellular sources in vivo are not clearly defined. By using immunohistochemical staining and analysis of chemokine mRNA expression, the present study aimed to localize cells producing MIP-2 in tissues of normal mice and mice challenged with Yersinia enterocolitica. The results showed a constitutive expression of MIP-2 mRNA in bone marrow (BM) of normal mice, but not in other organs such as spleen, lung, or liver. MIP-2 protein was found in all organs tested but it was exclusively associated with PMNs that stained positive with the cell surface marker Gr-1. Bacterial infection caused a 5-fold increase in the number of MIP-2-positive PMNs recruited to spleens concomitant with a strong increase of splenic MIP-2 mRNA. This correlated well with a 3-fold loss of MIP-2-producing cells in BM. Because MIP-2 mRNA expression in PMNs was increased after stimulation with TNF, the results indicate that newly recruited PMNs can supplement their MIP-2 content through TNF-stimulated transcription. Together, the data imply a constitutive production of MIP-2 by a subset of PMNs in BM and argue for the possibility of a rapid mobilization of MIP-2 through its storage in circulating PMNs.

• Authors: S P Matzer, T Baumann, N W Lukacs, M Röllinghoff, H U Beuscher
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 167 Issue 8 Pg. 4635-43 (Oct 15 2001) ISSN: 0022-1767 [Print] United States
• PMID: 11591793 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chemokine CXCL2
• Chemokines
• Cxcl2 protein, mouse
• Interleukin-1
• RNA, Messenger
• Tumor Necrosis Factor-alpha

Topics

• Animals
• Bone Marrow Cells (chemistry, immunology)
• Chemokine CXCL2
• Chemokines (biosynthesis, genetics, isolation & purification)
• Chemotaxis, Leukocyte
• Female
• Granulocytes (chemistry)
• Interleukin-1 (pharmacology)
• Leukopoiesis
• Mice
• Mice, Inbred BALB C
• Neutrophils (chemistry, immunology)
• RNA, Messenger (isolation & purification)
• Spleen (cytology, immunology)
• Tissue Distribution
• Tumor Necrosis Factor-alpha (pharmacology)
• Yersinia Infections (immunology)
• Yersinia enterocolitica