Constitutive expression of CXCL2/MIP-2 is restricted to a Gr-1high, CD11b+, CD62Lhigh subset of bone marrow derived granulocytes

CXCL2/macrophage inflammatory protein (MIP)-2 is an inducible murine chemokine involved in attraction of polymorphonuclear granulocytes to sites of infection. In comparison, its role as constitutive produced chemokine in mice is unclear. The present study aimed to specify the cellular source of constitutively produced CXCL2/MIP-2 and to examine its expression pattern in comparison to other chemokines in peripheral lymphoid tissues as well as bone marrow (BM) of normal mice. The results showed that constitutive expression of CXCL2/MIP-2 mRNA was restricted to BM. As revealed by RT-PCR and FACS analysis, CXCL2/MIP-2 production was restricted to a specialized subset of BM derived Gr-1(high) granulocytes. This subset was characterized by surface expression of CD11b(+), CD62L(high) and CXCR2(+) and accounted for 4-6% of total BM cells. In vitro stimulation of BM cells did not increase the number of CXCL2/MIP-2(+) granulocytes. Intracellular CXCL2/MIP-2 was not strictly correlated to surface expression of its receptor, as the majority of the CXCR2(+)/Gr-1(high) cells lacked CXCL2/MIP-2 staining. In controls, CXCL1/KC expression was not detected in BM but was found in peripheral tissues in the absence of CXCL2/MIP-2. Together, our results show that CXCL2/MIP-2 and CXCL1/KC are differentially expressed in a tissue specific manner in normal mice and that CXCL2/MIP-2 is produced in a well-defined CD11b(+), CD62L(high), Gr-1(high) subset of BM granulocytes, thereby providing a possible explanation for the independent regulation of both chemokines.