Constitutive Expression of Macrophage-Inflammatory Protein 2 (MIP-2) mRNA in Bone Marrow Gives Rise to Peripheral Neutrophils with Preformed MIP-2 Protein

• Published in: The Journal of immunology (1950) Vol. 167; no. 8; pp. 4635 - 4643
• Main Authors: Matzer, Sigrid P, Baumann, Tobias, Lukacs, Nicholas W, Rollinghoff, Martin, Beuscher, H. Ulrich
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15-10-2001
• Subjects: Animals; Bone Marrow Cells - chemistry; Bone Marrow Cells - immunology; Chemokine CXCL2; Chemokines - biosynthesis; Chemokines - genetics; Chemokines - isolation & purification; Chemotaxis, Leukocyte; Female; Granulocytes - chemistry; Interleukin-1 - pharmacology; Leukopoiesis; Macrophage inflammatory protein 2; Mice; Mice, Inbred BALB C; Neutrophils - chemistry; Neutrophils - immunology; RNA, Messenger - isolation & purification; Spleen - cytology; Spleen - immunology; Tissue Distribution; Tumor Necrosis Factor-alpha - pharmacology; Yersinia enterocolitica; Yersinia Infections - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.167.8.4635

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.