Constitutive expression of macrophage-inflammatory protein 2 (MIP-2) mRNA in bone marrow gives rise to peripheral neutrophils with preformed MIP-2 protein.
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.
Matzer
S P
SP
Institute for Clinical Microbiology, Immunology, and Hygiene, University of Erlangen, Erlangen, Germany.
Baumann
T
T
Lukacs
N W
NW
Röllinghoff
M
M
Beuscher
H U
HU
D000818:Animals; D001854:Bone Marrow Cells / Q000737:chemistry* / Q000276:immunology; D054426:Chemokine CXCL2; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification*; D002634:Chemotaxis, Leukocyte; D005260:Female; D006098:Granulocytes / Q000737:chemistry; D007375:Interleukin-1 / Q000494:pharmacology; D019891:Leukopoiesis; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000737:chemistry* / Q000276:immunology; D012333:RNA, Messenger / Q000302:isolation & purification; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014018:Tissue Distribution; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015009:Yersinia Infections / Q000276:immunology; D015008:Yersinia enterocolitica
D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha