CCL3 and CXCL12 regulate trafficking of mouse bone marrow NK cell subsets.
Herein we have analyzed chemokine involvement in the trafficking of developing and mature mouse natural killer (NK) cells in the bone marrow (BM). We observed drastic changes of CCR1, CXCR3, and CXCR4 expression and function during progression from precursor NK (pNK) cells to immature DX5- NK (iNK) and mature DX5+ NK (mNK) cells. pNK and mNK cells expressed the 3 receptors, while only CXCR4 was detected on iNK cells. Correspondingly, mNK cells migrated to CXCL12, CXCL10, and CCL3, and pNK and iNK cells to CXCL12, whereas pNK cells migrated to CCL3 and CXCL10 only after CXCL12 stimulation. Comparison of BM, peripheral blood, and spleen mNK cell populations revealed that CXCL12, CXCL10, and CCL3 preferentially affected BM mNK cell migration. Administration of the CXCR4 antagonist, AMD-3100, to C57BL/6 mice induced strong reduction of mNK and iNK cells in the BM and increased their number in blood and spleen. Conversely, CCL3 administration selectively mobilized mNK cells from the BM and this effect correlated with its ability to inhibit CXCL12-mediated mNK cell responses in vitro. Our results suggest that the combined action of chemokines selectively regulates localization of NK cell subsets in the BM and direct their maturation and migration to the periphery.
Bernardini
Giovanni
G
Department of Experimental Medicine-Istituto Pasteur-Fondiazone Cenci Bolognetti, University of Rome La Sapienza, Italy. giovanni.bernardini@uniroma1.it
Sciumè
Giuseppe
G
Bosisio
Daniela
D
Morrone
Stefania
S
Sozzani
Silvano
S
Santoni
Angela
A
D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology; D001596:Benzylamines; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology*; D054405:Chemokine CCL3 / Q000276:immunology; D054357:Chemokine CXCL10 / Q000276:immunology; D054377:Chemokine CXCL12 / Q000276:immunology; D000080027:Cyclams; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D006571:Heterocyclic Compounds / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D051379:Mice; D009928:Organ Specificity / Q000187:drug effects / Q000276:immunology; D054389:Receptors, CCR1 / Q000276:immunology; D054367:Receptors, CXCR3 / Q000276:immunology; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000276:immunology; D013234:Stem Cells / Q000166:cytology / Q000276:immunology
D019380:Anti-HIV Agents; D001596:Benzylamines; C514936:CXCR4 protein, mouse; C496534:Ccl3 protein, mouse; C515301:Ccr1 protein, mouse; D054405:Chemokine CCL3; D054357:Chemokine CXCL10; D054377:Chemokine CXCL12; C485433:Cxcl10 protein, mouse; C515256:Cxcl12 protein, mouse; C515188:Cxcr3 protein, mouse; D000080027:Cyclams; D006571:Heterocyclic Compounds; D054389:Receptors, CCR1; D054367:Receptors, CXCR3; D019718:Receptors, CXCR4; C088327:plerixafor