Cloning and Characterization of a Novel Murine β Chemokine Receptor, D6

The β-chemokine macrophage inflammatory protein-1α (MIP-1α) is chemotactic for many hemopoietic cell types and can inhibit hemopoietic stem cell (HSC) proliferation, effects mediated through G-protein coupled heptahelical receptors. We have isolated cDNAs for seven chemokine receptors, CCR-1 to -5, MIP-1αRL1, and a novel cDNA, D6. Chinese hamster ovary cells expressing CCR-1, -3, -5, and D6 bound 125I-murine MIP-1α: the order of affinity was D6 > CCR-5 > CCR-1 > CCR-3. Each bound a distinct subset of other β-chemokines: the order of competition for 125I-murine MIP-1α on D6 was murine MIP-1α > human and murine MIP-1β > human RANTES∼JE > human MCP-3 > human MCP-1. Human MIP-1α and the α-chemokines did not compete. Like other chemokine receptors, D6 induced transient increases in Ca2+ in HEK 293 cells upon ligand binding. D6 mRNA was abundant in lung and detectable in many other tissues. Bone marrow cell fractionation demonstrated T-cell and macrophage/monocyte expression of D6, and CCR-1, -3, and -5. Moreover, we could detect expression of CCR-3, CCR-5, and to a greater extent D6 in a cell population enriched for HSCs. Thus, we have characterized four murine β chemokine receptors that are likely involved in mediating the pro-inflammatory functions of MIP-1α and other chemokines, and we present D6, CCR-3, and CCR-5 as candidate receptors in MIP-1α-induced HSC inhibition. The β-chemokine macrophage inflammatory protein-1α (MIP-1α) is chemotactic for many hemopoietic cell types and can inhibit hemopoietic stem cell (HSC) proliferation, effects mediated through G-protein coupled heptahelical receptors. We have isolated cDNAs for seven chemokine receptors, CCR-1 to -5, MIP-1αRL1, and a novel cDNA, D6. Chinese hamster ovary cells expressing CCR-1, -3, -5, and D6 bound 125I-murine MIP-1α: the order of affinity was D6 > CCR-5 > CCR-1 > CCR-3. Each bound a distinct subset of other β-chemokines: the order of competition for 125I-murine MIP-1α on D6 was murine MIP-1α > human and murine MIP-1β > human RANTES∼JE > human MCP-3 > human MCP-1. Human MIP-1α and the α-chemokines did not compete. Like other chemokine receptors, D6 induced transient increases in Ca2+ in HEK 293 cells upon ligand binding. D6 mRNA was abundant in lung and detectable in many other tissues. Bone marrow cell fractionation demonstrated T-cell and macrophage/monocyte expression of D6, and CCR-1, -3, and -5. Moreover, we could detect expression of CCR-3, CCR-5, and to a greater extent D6 in a cell population enriched for HSCs. Thus, we have characterized four murine β chemokine receptors that are likely involved in mediating the pro-inflammatory functions of MIP-1α and other chemokines, and we present D6, CCR-3, and CCR-5 as candidate receptors in MIP-1α-induced HSC inhibition. Macrophage inflammatory protein-1α (MIP-1α) 1The abbreviations used are: MIP, macrophage inflammatory protein; IL, interleukin; MCP, monocyte chemoattractant protein; RANTES, regulated on activation, normal T cell expressed and secreted; CCR, C-C chemokine receptor; CHO, Chinese hamster ovary; FCS, fetal calf serum; RT, reverse transcriptase; PCR, polymerase chain reaction; m, murine; h, human; RACE, rapid amplification of cDNA ends; lin−, lineage negative; PBS, phosphate-buffered saline. is a member of the chemokine family, a group of almost 30 small polypeptides related functionally with respect to their ability to act as stimulators of leukocyte chemotaxis, and structurally due to the conservation of four disulfide-forming cysteine residues (reviewed in Refs. 1Schall T.J. Cytokine. 1991; 3: 165-183Crossref PubMed Scopus (659) Google Scholar, 2Oppenheim J.J. Zachariae C.O.C. Mukaida N. Matsushima K. Annu. Rev. Immunol. 1991; 9: 617-648Crossref PubMed Scopus (1871) Google Scholar, 3Kunkel S.L. Strieter R.M. Lindley I.J.D. Westwick J. Immunol. Today. 1995; 16: 559-561Abstract Full Text PDF PubMed Scopus (111) Google Scholar, 4Murphy P.M. Cytokine Growth Factor Rev. 1996; 7: 47-64Crossref PubMed Scopus (285) Google Scholar, 5Power C.A. Wells T.N.C. Trends Pharmocol. Sci. 1996; 17: 209-213Abstract Full Text PDF PubMed Scopus (77) Google Scholar). Variation in this structural motif allows the family to be subdivided into two main branches. The C-X-C or α chemokines, which include interleukin-8 (IL-8), macrophage inflammatory protein-2α and -β (MIP-2α and -β), and KC, have a single amino acid residue separating the two most amino-terminal cysteines. In the C-C or β branch these two cysteines are juxtaposed: macrophage inflammatory protein-1α and -β (MIP-1α and -β), monocyte chemoattractant proteins 1, 2, 3, and 4 (MCP-1, 2, 3, and 4), C10, eotaxin and RANTES are all members of this subfamily. Lymphotactin, a C chemokine, is unique in containing only a single amino-terminal cysteine residue, and only two in the mature protein (6Kelner G.S. Kennedy J. Bacon K.B. Kleyensteuber S. Largaespada D.A. Jenkins N.A. Copeland N.G. Bazan J.F. Moore K.W. Schall T.J. Zlotnik A. Science. 1994; 266: 1395-1399Crossref PubMed Scopus (632) Google Scholar). This also appears to represent a functional division as there is no sharing of signaling receptors between the subfamilies and while α-chemokines are classically viewed as neutrophil chemotaxins, the β family stimulate monocyte and macrophage migration and function (1Schall T.J. Cytokine. 1991; 3: 165-183Crossref PubMed Scopus (659) Google Scholar, 2Oppenheim J.J. Zachariae C.O.C. Mukaida N. Matsushima K. Annu. Rev. Immunol. 1991; 9: 617-648Crossref PubMed Scopus (1871) Google Scholar, 3Kunkel S.L. Strieter R.M. Lindley I.J.D. Westwick J. Immunol. Today. 1995; 16: 559-561Abstract Full Text PDF PubMed Scopus (111) Google Scholar, 4Murphy P.M. Cytokine Growth Factor Rev. 1996; 7: 47-64Crossref PubMed Scopus (285) Google Scholar, 5Power C.A. Wells T.N.C. Trends Pharmocol. Sci. 1996; 17: 209-213Abstract Full Text PDF PubMed Scopus (77) Google Scholar). Eosinophils, basophils, and lymphocytes migrate in response to certain members of both families, that in some cases induce more overt inflammatory functions such as a respiratory burst or degranulation (7Baggiolini M. Dahinden C.A. Immunol. Today. 1994; 15: 127-133Abstract Full Text PDF PubMed Scopus (522) Google Scholar, 8Taub D.D. Conlon K. Lloyd A.R. Oppenheim J.J. Kelvin D.J. Science. 1993; 260: 355-358Crossref PubMed Scopus (714) Google Scholar, 9Taub D.D. Sayers T.J. Carter C.R.D. Ortaldo J.R. J. Immunol. 1995; 155: 3877-3888PubMed Google Scholar, 10Schweizer R.C. Welmers B.A.C. Raaijmakers J.A.M. Zanen P. Lammers J.-W.J. Koenderman L. Blood. 1994; 83: 3697-3704Crossref PubMed Google Scholar, 11Schall T.J. Bacon K. Toy K.J. Goeddel D.V. Nature. 1990; 347: 669-671Crossref PubMed Scopus (1299) Google Scholar, 12Dahinden C.A. Kurimoto Y. de Weck A.L. Lindley I. Dewald B. Baggiolini M. J. Exp. Med. 1989; 170: 1787-1792Crossref PubMed Scopus (147) Google Scholar, 13Larsen C.G. Anderson A.O. Appella E. Oppenheim J.J. Matsushima K. Science. 1989; 243: 1464-1466Crossref PubMed Scopus (987) Google Scholar). Thus, these proteins are likely to be crucial during leukocyte trafficking and immune surveillance, and have been implicated in the development of various allergic responses, such as asthma (14Rothenberg M.E. Luster A.D. Lilly C.M. Drazen J.M. Leder P. J. Exp. Med. 1995; 181: 1211-1216Crossref PubMed Scopus (198) Google Scholar), and in inflammatory diseases like rheumatoid arthritis (15Hosaka S. Akahoshi T. Wada C. Kondo H. Clin. Exp. Immunol. 1994; 97: 451-457Crossref PubMed Scopus (153) Google Scholar) and chronic lung inflammation (16Driscoll K.E. Exp. Lung Res. 1994; 20: 473-490Crossref PubMed Scopus (273) Google Scholar). Mice lacking the MIP-1α gene do not exhibit a normal immune response when infected with certain viruses, such as cocksackie virus in which the with this virus is not S.L. J.F. Science. 1995; PubMed Scopus Google Scholar). This to the in of MIP-1α as a of inflammatory The have also been implicated in the of the during S.L. Strieter R.M. Science. PubMed Scopus Google Scholar, G.S. J. A.L. Science. 1990; PubMed Scopus Google Scholar, A.L. C. D.D. J.M. S. J. Exp. Med. 1995; PubMed Scopus Google Scholar), and in the of cell H. M. M. 1994; PubMed Scopus Google Scholar, S. C. 1994; Google Scholar, T. Sci. S. A. 1995; PubMed Scopus Google Scholar, K.B. P. Schall T.J. Science. 1995; PubMed Scopus Google Scholar, J. J. M. C. M. Blood. 1995; PubMed Google Scholar, S. Nature. 1990; PubMed Scopus Google Scholar, P. C. M. J. 1993; Full Text PDF PubMed Google Scholar). lacking the α chemokine have of and marrow cells T. S. K. N. Y. N. H. T. Nature. 1996; PubMed Scopus Google Scholar), while lacking the murine have of J. K. S. B. Moore Science. 1994; PubMed Scopus Google Scholar), these two proteins in the of cell We have demonstrated that and to a extent are to inhibit the of hemopoietic stem cells both in and in S. Nature. 1990; PubMed Scopus Google Scholar). MIP-1α is also as a of cell proliferation, with the of the chemokine the cells P. C. M. J. 1993; Full Text PDF PubMed Google Scholar). have been on the of human hemopoietic stem cells and on a of cell that to have a affinity for MIP-1α present on more mature cell types L. M. Growth 1993; Google Scholar, K.J. Blood. 1994; PubMed Google Scholar, J.R. E. M. J.M. Blood. 1994; PubMed Google Scholar). We have that the hemopoietic stem cell is distinct the monocyte a of which is in stem cell is to induce monocyte S. A. J. 1996; 15: PubMed Scopus Google Scholar). of chemokine receptors, all members of the heptahelical have been which are to of the α or β (reviewed in Refs. 4Murphy P.M. Cytokine Growth Factor Rev. 1996; 7: 47-64Crossref PubMed Scopus (285) Google and 5Power C.A. Wells T.N.C. Trends Pharmocol. Sci. 1996; 17: 209-213Abstract Full Text PDF PubMed Scopus (77) Google Scholar). Human CCR-1, and RANTES and is expressed on all mature hemopoietic cell types K. Schall T.J. 1993; Full Text PDF PubMed Scopus Google Scholar, A. L. K. Oppenheim J.J. J.M. J. 1995; Full Text Full Text PDF PubMed Scopus Google Scholar, C. J. P.M. J. 1995; Full Text Full Text PDF PubMed Scopus Google Scholar). Human which is expressed on and some can be as two both of which and in response to and MCP-3 with the G-protein C. J. P.M. J. 1995; Full Text Full Text PDF PubMed Scopus Google Scholar, A. C. Sci. S. A. 1994; PubMed Scopus Google Scholar, Y. Y. H. J. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar). in the of human and murine CCR-3, and P.M. Cytokine Growth Factor Rev. 1996; 7: 47-64Crossref PubMed Scopus (285) Google Scholar, 5Power C.A. Wells T.N.C. Trends Pharmocol. Sci. 1996; 17: 209-213Abstract Full Text PDF PubMed Scopus (77) Google Scholar). Human CCR-5, which as a affinity for and RANTES, is a of the protein for the of and many of the human and -3, and the also act as for C. Y. Kennedy P.M. Science. 1996; PubMed Scopus Google Scholar, H. M. Y. N. B. L. N. C. J. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar, H. S. M. P. S. C.M. Schall T.J. Nature. 1996; PubMed Scopus Google Scholar, J. Y. M. M. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar, T. Y. C. Moore Nature. 1996; PubMed Scopus Google Scholar, M. H. C. I. J. Nature. 1996; PubMed Scopus Google Scholar). The CCR-5 are to the of cells with human virus A.L. A. R.C. P. Science. 1996; Scopus Google Scholar), that these proteins in the of cells for a of CCR-5 are to with certain human virus M. J. C. S. C. J. C. C. M. T. S. Y. M. Nature. 1996; PubMed Scopus Google Scholar). the of of we have seven murine members of the β-chemokine family, and novel D6. of these D6, proteins of to murine MIP-1α when expressed in Chinese hamster ovary cells with to D6 appears to be the affinity murine MIP-1α to The of murine and human and murine that the with is mediated amino acid residues in the the of other that are to with the four MIP-1α receptors is and the of sharing that the β-chemokine We have also expression for of the receptors and their expression in many hemopoietic cell In we present a subset of these receptors in the of stem cell inhibition. and the with and was polymerase and on was on in human and and murine eotaxin to the of murine MIP-1α to we have a of of the which are more for of the J. S. A. J. J. 1994; Full Text PDF PubMed Google Scholar). of these is used this and be to as cell cells in with 4 and fetal calf HEK 293 cells in with and 4 cells as S. K. K. A. J. Immunol. 1995; Google Scholar). The of between human CCR-1 and and in the of was isolated the of a to J. T. Scholar). was of to of and of and for for for and for of into and and rapid amplification of cDNA was to their on or cell for in of the with human A. C. Sci. S. A. 1994; PubMed Scopus Google Scholar) was used on cDNA or to the with containing and and to the and of the and all into and in both J. P. Res. Scopus Google the and was to K. 1993; PubMed Scopus Google Scholar). with the and the for to to and in to was the reverse was in two with and reverse of was used which been with to to and used and for for 30 of for for for cDNAs the and into into cells and single cell in as S. A. J. 1996; 15: PubMed Scopus Google Scholar). was to expression and of the for ligand containing D6 cDNA was into HEK 293 cells to the of cells in of on a with as L. M. Growth 1993; Google Scholar). cells in and with PBS, the cells in of fetal calf 4 containing of MIP-1α and for was in and the cell was the of of cells to a and bound for in a Each was in and for was and in PubMed Scopus Google Scholar). cell and the cell was for and 4 cells that a in to a with in with the of while the with other HEK 293 cells with D6 in and in containing for in the in to and to in was in a in a to and and to a of Bone marrow cells the of isolated into containing fetal calf cells used for mRNA The cells to of and for 30 The cells the for a through the in and to in cell types in the order of and with to the the four cell cells lineage mRNA was isolated the cell and the and cDNA to the with the cDNA was with the was and the cDNA and of as used for cDNA to and and and and and lineage and Each of of for and to 4 in containing and of with of for The was for to to to the and The the cDNA to J. T. Scholar), in containing and for cDNA to and on a the was in a of was on of this in a containing of of the cell and of for for for and for of the population of cells on a that was for with and for 30 in was to and as for in to cDNA was used as a for of the chemokine receptors. used murine T cell cDNA and murine cDNA M. of murine M. A. murine cDNA and murine of the and two we of seven members of the murine family which used to cDNAs of are with a amino acid to murine chemokine receptors, is CCR-1, is to human is CCR-3, is is CCR-5, and is the P.M. J. 1995; Full Text Full Text PDF PubMed Scopus Google Scholar, M.E. Luster A.D. N. C. J. Immunol. 1995; 155: Google Scholar, Wells T.N.C. C.A. Res. 1995; Scopus Google Scholar, L. J. J. 1996; Full Text Full Text PDF PubMed Scopus (111) Google Scholar, A. Wells T.N.C. C.A. J. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar). In we have also a novel D6, which to these and other members of the of chemokine receptors. D6 cDNA, isolated a single a protein of amino and that represent for this gene with a in the to This be to of related to the receptors, in which two distinct in the of or of the L. M. A. Baggiolini M. B. J. 1995; PubMed Scopus Google Scholar). to the with the other receptors. we the that these D6 are the of The D6 protein the the four cysteine residues to the in a and in a single the amino In with other chemokine receptors, the amino is the amino are to a that is not in the related chemokine receptors. for protein is present on the and for protein C and are in the which a of and The motif in the which is involved in G-protein is to in D6, a which likely the of G-protein D6 the present in many heptahelical receptors the of the or is a amino acid and is amino 1994; Google Scholar). a the amino-terminal of the which is not present in many of the other chemokine receptors of the between D6 and the other chemokine receptors that D6 some and to of the chemokine receptors not that this between the C-C and C-X-C most related to and two murine J. K. S. B. Moore Science. 1994; PubMed Scopus Google Scholar) and of amino to be in ligand that in this D6 is more related to the C-C chemokine receptors, CCR-1 not of D6 expression that expression of a single for D6 was detectable in and in and In expression of D6 in and not or also detectable in murine for CCR-1 > > > lung > > and CCR-5 in not or not be that the of to the in many of these be and of the cell expression in of these in in the of MIP-1α receptors, of the seven receptors was into cells and expressing for their ability to CCR-1, CCR-3, CCR-5, and D6 bound and we have on these four receptors. been to human MIP-1α Wells T.N.C. C.A. Res. 1995; Scopus Google Scholar) and to detect with murine MIP-1α is and that can between MIP-1α these two we have not demonstrated cell expression of in the cell The for the receptors as allows the of the receptors into affinity and and affinity and also present D6 as the affinity for MIP-1α to and that these two can also be on the of their ability to human MIP-1α and CCR-5 and D6 only or no of with human RANTES of and CCR-1 and both human MIP-1α with to that with no with is for of to cells expressing CCR-1, CCR-3, CCR-5, and for cells expressing of the receptors in for in containing a of to containing of also with PBS, in and in a for PubMed Scopus Google Scholar). are of in in which the of was the and of in the to the in a in for upon with CCR-1, CCR-3, CCR-5, and D6, in which no of was detectable of ligand of CCR-5 and or CCR-1 and in which no of was detectable of ligand of CCR-5 and or CCR-1 and PubMed Scopus Google Scholar) to of the between ligand and in in which no of was detectable of ligand of CCR-5 and or CCR-1 and in a cells expressing of the receptors in for in containing a of to containing of also with PBS, in and in a for PubMed Scopus Google Scholar). are of in in which the of was the and of in the to the PubMed Scopus Google Scholar) to of the between ligand and in these four receptors murine and human MIP-1β with human murine and human MCP-3 also to D6 with in the while CCR-5 also with human and murine and human C and CCR-1 also with and murine when the ligand is present 4 Thus, of the four MIP-1α receptors a unique of the of which only with CCR-1, for is of the α-chemokines and are of MIP-1α of the chemokine receptors that these receptors are for the β-chemokine This is with respect to D6 the of between this and the and β-chemokine receptors. which been as a ligand for M. M.E. P.M. Luster A.D. Res. 1996; PubMed Scopus Google Scholar), to with the and of not Thus, D6 as a affinity for when is expressed in to > human and murine MIP-1β > > > The affinity and of this most that with CCR-5, while CCR-1 and with affinity to and are more for human and murine MIP-1α and upon ligand is of chemokine receptors to to the in of cells expressing of the receptors to a upon chemokine of HEK 293 cells with D6 HEK 293 cells have been used to chemokine of with or a detectable in that this is to upon ligand a response In of the to the cells to a with a D6 ligand HEK 293 cells to all the not more the of expression the hemopoietic we have the expression of D6 and the other MIP-1α receptors cDNA of hemopoietic a lineage containing cells We have the of this of the cell cDNA with lineage The a of lineage and a of cells in the due to of the cDNA to amplification and We have these cDNA for of expression of the four murine MIP-1α chemokine receptors, and The this in expression of all the receptors in the T cell and CCR-1, -3, and CCR-5 are also expressed in the In to and we have also been to detect CCR-1 and D6 expression in the cell that these receptors be a normal of the cell a of the MIP-1α receptors are also detectable in lineage hemopoietic cells a for these in MIP-1α-induced stem cell D6 is a in cells to marrow to to that with CCR-3, and CCR-5, are also detectable and the are in the cell population in marrow and the In the present we have seven murine chemokine receptors, a novel cDNA which we have D6. of these D6, proteins in cells which to and have demonstrated that these receptors also distinct of other D6 is a and can a transient in upon with In we have characterized the expression of of the receptors, T-cell and expression of the four MIP-1α receptors, and have the expression of D6, and and in a stem marrow of the of D6 and the other chemokine receptors that is related to the and Thus, D6 structurally represent a member of a subset of chemokine receptors. This is in the of chemokine receptors, such as the motif the amino-terminal of the that is to in D6 the of this and the G-protein during is and signaling that functions as a which This in be mediated the amino of D6 which more to β-chemokine receptors, CCR-1, receptors. D6 cDNA expressed in cells the affinity murine MIP-1α to and many with This protein also with affinity to human and murine MIP-1β and human RANTES we to D6 and CCR-5 with human the human and proteins and human RANTES are a of residues are that are in human are of with in to in and to in that the these We have a of murine J. S. A. J. J. 1994; Full Text PDF PubMed Google Scholar), in which the residue been to this in J. S. A. J. J. 1994; Full Text PDF PubMed Google Scholar), and with affinity to D6 not the the of in have a more on The the residue to the residue in is a candidate for in the in to D6 with murine and human MIP-1α: the in and of the chain a in this of the on the of J. Science. 1994; PubMed Scopus Google Scholar, J. Schall T.J. 1995; PubMed Scopus Google Scholar) in the and are likely to be on the of the protein in and act as a and with in are also involved in to D6 as of these residues in S. A. J. 1996; 15: PubMed Scopus Google Scholar) the affinity of for this with the to not residues are not as are also in Thus, there be of involved in mediating affinity to D6, and in these effects on the ability of the ligand to the in the of D6 and CCR-5, is likely that the residues in that to CCR-5 be the as for D6. D6 is also to with and human that this is with respect to ligand that can also to D6, with a in the not In CCR-1 and to be more for MIP-1α and -β have affinity for these CCR-5 and D6. human RANTES did not these two receptors, which is in with CCR-1 P.M. J. 1995; Full Text Full Text PDF PubMed Scopus Google Scholar, M.E. Luster A.D. N. C. J. Immunol. 1995; 155: Google Scholar) this chemokine with of 4 M.E. Luster A.D. N. C. J. Immunol. 1995; 155: Google Scholar). The for this is there are a of expression in cell types or G-protein that ligand we used cells in this while cells M.E. Luster A.D. N. C. J. Immunol. 1995; 155: Google Scholar) or cells P.M. J. 1995; Full Text Full Text PDF PubMed Scopus Google Scholar) used there are amino acid between for CCR-1 and and of of is in the and binding. this of CCR-1 appears to be in mediating ligand and L. J. J. 1996; Full Text Full Text PDF PubMed Scopus (111) Google J. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar). human and murine MIP-1α and and as a for human and murine eotaxin M. M.E. P.M. Luster A.D. Res. 1996; PubMed Scopus Google Scholar) we have been to eotaxin due to the of this chemokine to with and M. M.E. P.M. Luster A.D. Res. 1996; PubMed Scopus Google Scholar) to detect in response to and -β in HEK 293 cells with CCR-3, eotaxin could into these is the proteins are to a upon with or are to eotaxin to CCR-3. the of this in the T-cell and cells upon which eotaxin no This that signaling to in other functions in and in response to the is of that the of these four murine receptors exhibit a of with their human and the between structural and functional of murine more of and functional In with these we have demonstrated that all the four MIP-1α receptors are expressed in cells of the and T-cell cell types these these proteins to be that cells distinct of or with certain present a of MIP-1α receptors which could to only to certain of ligand or We have that MIP-1α is to inhibit the of hemopoietic stem cells and cells S. Nature. 1990; PubMed Scopus Google Scholar, P. C. M. J. 1993; Full Text PDF PubMed Google Scholar). of the four MIP-1α receptors is in murine not marrow have demonstrated that for hemopoietic stem cells in a for cells expressing D6, and and -5. receptors also to not a that stem cell is in monocyte S. A. J. 1996; 15: PubMed Scopus Google Scholar). to of the in hemopoietic stem cell be to the expression of the in the cell to and other chemokines, is are in We M. for cell for of the and for cDNA for the cell and for the HEK 293 cells and on We also for this also for