Alpha and beta chemokines induce NK cell migration and enhance NK-mediated cytolysis.
Chemokines have been shown to play an important role in both the adhesion and migration of numerous leukocytic cell types, including granulocytes, monocytes, mast cells, and T lymphocytes. However, the biologic effects of chemokines on NK cells remain to be defined. Chemotaxis studies using purified human NK cells and a panel of human recombinant chemokines revealed that macrophage inflammatory protein (MIP)-1 alpha and IFN-inducible protein-10 (IP-10) are potent NK cell chemoattractants in vitro. Modest but significant chemotactic (not chemokinetic) responses were also observed in response to RANTES, MCP-1, MCP-2, MCP-3, and MIP-1 beta. Chemokine receptor expression on human NK cells was determined through displacement and Scatchard analyses, using a panel of radiolabeled chemokines, and revealed the presence of both distinct and shared chemokine receptors with affinities similar to those previously described for other cell types. Functional studies have also revealed that the beta chemokines and IP-10 are capable of augmenting NK- but not LAK- or ADCC-specific cytolytic responses in both a dose- and donor-dependent fashion. Neutralization analysis using Abs specific for various adhesion molecules revealed that NK:tumor cell conjugate formation is required for chemokine-induced NK killing. In addition, NK cells incubated in the presence of beta chemokines and IP-10 for 4 h induced the release of granule-derived serine esterases, suggesting a possible mechanism for chemokine-mediated NK killing. These results suggest that chemokines not only play an important role in the recruitment of NK cells, but also may be important mediators of NK cell degranulation augmenting local tumor cell destruction.
Taub
D D
DD
Clinical Support Laboratory, SAIC-Frederick, National Cancer Institute-FCRDC, MD 21702, USA.
Sayers
T J
TJ
Carter
C R
CR
Ortaldo
J R
JR
D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D018932:Chemokine CCL2 / Q000494:pharmacology; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000494:pharmacology; D054357:Chemokine CXCL10; D018925:Chemokines / Q000494:pharmacology*; D019743:Chemokines, CXC; D016207:Cytokines / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004950:Esterases / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D019402:Macrophage Inflammatory Proteins; D015846:Monokines / Q000494:pharmacology
D018932:Chemokine CCL2; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D018925:Chemokines; D019743:Chemokines, CXC; D016207:Cytokines; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D004950:Esterases; C022635:serine esterase