Dual functions of fractalkine/CX3C ligand 1 in trafficking of perforin+/granzyme B+ cytotoxic effector lymphocytes that are defined by CX3CR1 expression.
Fractalkine/CX3C ligand 1 and its receptor CX3CR1 are known to mediate both cell adhesion and cell migration. Here we show that CX3CR1 defines peripheral blood cytotoxic effector lymphocytes commonly armed with intracellular perforin and granzyme B, which include NK cells, gammadelta T cells, and terminally differentiated CD8(+) T cells. In addition, soluble fractalkine preferentially induced migration of cytotoxic effector lymphocytes. Furthermore, interaction of cytotoxic effector lymphocytes with membrane-bound fractalkine promoted subsequent migration to the secondary chemokines, such as macrophage inflammatory protein-1beta/CC ligand 4 or IL-8/CXC ligand 8. Thus, fractalkine expressed on inflamed endothelium may function as a vascular regulator for cytotoxic effector lymphocytes, regardless of their lineage and mode of target cell recognition, through its ability to capture them from blood flow and to promote their emigration in response to other chemokines.
Nishimura
Miyuki
M
Kan Research Institute, Kyoto, Japan.
Umehara
Hisanori
H
Nakayama
Takashi
T
Yoneda
Osamu
O
Hieshima
Kunio
K
Kakizaki
Mayumi
M
Dohmae
Naochika
N
Yoshie
Osamu
O
Imai
Toshio
T
D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000097:blood; D000073883:CX3C Chemokine Receptor 1; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000502:physiology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D053804:Granzymes; D006801:Humans; D007424:Intracellular Fluid / Q000201:enzymology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D008565:Membrane Proteins / Q000502:physiology*; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D011485:Protein Binding / Q000276:immunology; D051381:Rats; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000096:biosynthesis*; D015728:Receptors, HIV / Q000096:biosynthesis*; D012697:Serine Endopeptidases / Q000096:biosynthesis*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology* / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*
D015415:Biomarkers; D000073883:CX3C Chemokine Receptor 1; C515538:CX3CL1 protein, human; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; C515540:Cx3cl1 protein, rat; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D052899:Pore Forming Cytotoxic Proteins; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D015728:Receptors, HIV; D054353:Perforin; C509213:GZMB protein, human; D053804:Granzymes; C509215:Gzmb protein, rat; D012697:Serine Endopeptidases