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Investigation of Macrophage Polarization Using Bone Marrow Derived Macrophages
Published on: June 23, 2013
Constitutive expression of macrophage-inflammatory protein 2 (MIP-2) mRNA in bone marrow gives rise to peripheral
S P Matzer1, T Baumann, N W Lukacs
1Institute for Clinical Microbiology, Immunology, and Hygiene, University of Erlangen, Erlangen, Germany.
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.
Insights
Macrophage-inflammatory protein 2 (MIP-2) is constitutively produced by bone marrow polymorphonuclear neutrophils (PMNs). Bacterial infection mobilizes these MIP-2-storing PMNs, increasing chemokine levels at inflammation sites.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Macrophage-inflammatory protein 2 (MIP-2) is a key CXC chemokine regulating polymorphonuclear neutrophil (PMN) migration during inflammation.
- The in vivo cellular sources of MIP-2 remain incompletely understood despite in vitro studies.
Purpose of the Study:
- To identify the specific cell types and tissues responsible for MIP-2 production in vivo.
- To investigate changes in MIP-2 expression and localization during bacterial infection.
Main Methods:
- Immunohistochemical staining to visualize MIP-2 protein and Gr-1+ PMNs.
- Analysis of chemokine mRNA expression in various tissues.
- Comparison of MIP-2 expression in normal and Yersinia enterocolitica-challenged mice.
Main Results:
- Constitutive MIP-2 mRNA expression was detected in bone marrow (BM), but not other organs, of normal mice.
- MIP-2 protein was primarily associated with Gr-1+ PMNs across all tested organs.
- Bacterial infection led to increased PMN recruitment and splenic MIP-2 mRNA, alongside a decrease in BM MIP-2-producing cells.
- TNF stimulation enhanced MIP-2 mRNA expression in PMNs, suggesting transcriptional regulation.
Conclusions:
- A subset of PMNs in the bone marrow constitutively produces MIP-2.
- Circulating PMNs can store and rapidly mobilize MIP-2 in response to inflammatory stimuli.
- Newly recruited PMNs may augment MIP-2 levels via TNF-stimulated transcription during infection.
