title: Regulation of human natural killer cell migration and proliferation by the exodus subfamily of CC chemokines.
abstract: Natural killer (NK) cells play an important role in innate and adaptive immune responses to obligate intracellular pathogens. Nevertheless, the regulation of NK cell trafficking and migration to inflammatory sites is poorly understood. Exodus-1/MIP-3alpha/LARC, Exodus-2/6Ckine/SLC, and Exodus-3/MIP-3beta/ELC/CKbeta-11 are CC chemokines that share a unique aspartate-cysteine-cysteine-leucine motif near their amino terminus and preferentially stimulate the migration of T lymphocytes. The effects of Exodus chemokines on human NK cells were examined. Exodus-1, -2, and -3 did not induce detectable chemotaxis of resting peripheral blood NK cells. In contrast, Exodus-2 and -3 stimulated migration of polyclonal activated peripheral blood NK cells in a dose-dependent fashion. Exodus-2 and -3 also induced dose-dependent chemotaxis of NKL, an IL-2-dependent human NK cell line. Results of modified checkerboard assays indicate that migration of NKL cells in response to Exodus-2 and -3 represents true chemotaxis and not simply chemokinesis. Exodus-1, -2, and -3 did not induce NK cell proliferation in the absence of other stimuli. Nevertheless, Exodus-2 and -3 significantly augmented IL-2-induced proliferation of normal human CD56(dim) NK cells. In contrast, Exodus-1, -2, and -3 did not affect the cytolytic activity of resting or activated peripheral blood NK cells. Expression of message for CCR7, a shared receptor for Exodus-2 and -3, was detected in activated polyclonal NK cells and NKL cells but not resting NK cells. Taken together, these results indicate that Exodus-2 and -3 can participate in the recruitment and proliferation of activated NK cells. Exodus-2 and -3 may regulate interactions between T cells and NK cells that are crucial for the generation of optimal immune responses.
authors.affiliation: Bone Marrow Transplantation Program and Division of Hematology/Oncology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. mjrobert@iupui.edu
authors.forename: M J
authors.initials: MJ
authors.lastname: Robertson
authors.forename: B T
authors.initials: BT
authors.lastname: Williams
authors.forename: K
authors.initials: K
authors.lastname: Christopherson
authors.forename: Z
authors.initials: Z
authors.lastname: Brahmi
authors.forename: R
authors.initials: R
authors.lastname: Hromas
mesh_terms: D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D054415:Chemokine CCL19; D054418:Chemokine CCL20; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects* / Q000276:immunology; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D015870:Gene Expression; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000166:cytology* / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D054399:Receptors, CCR6; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000235:genetics
chemical_list: C515460:CCL19 protein, human; C108355:CCL20 protein, human; C515478:CCL21 protein, human; C106311:CCR6 protein, human; C515370:CCR7 protein, human; D054415:Chemokine CCL19; D054418:Chemokine CCL20; D054421:Chemokine CCL21; D019742:Chemokines, CC; D007376:Interleukin-2; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D054399:Receptors, CCR6; D054400:Receptors, CCR7; D019707:Receptors, Chemokine