NK cell infiltration into lung, liver, and subcutaneous B16 melanoma is mediated by VCAM-1/VLA-4 interaction.
The mechanisms that regulate the adhesion and migration of NK cells to and across endothelium have been studied under nonflow conditions; however, the involvement of these processes in vivo is poorly understood. The present studies investigated the potential vascular adhesion ligand interactions that determine the in vivo recruitment of NK cells to pulmonary and hepatic parenchyma, and s.c. tumor after treatment of mice with biologic response modifiers. Seventy-two hours after a single injection of the cytokine-inducing agent poly-L-lysine stabilized in carboxylmethyl cellulose (poly-ICLC), pulmonary NK cell lytic activity and N-alpha-carbobenzoxy-L-lysine thiobenzyl ester (BLT)-esterase were augmented 29- and 14-fold, respectively, and the number of lung-associated NK cells was increased from 2.3 x 10(5) to 7.4 x 10(5). Similar fold increases in NK cell number and activity were observed in the liver and s.c. B16 melanoma after poly-ICLC injection or in the lungs and liver of mice treated with IL-2. Concomitant treatment of mice with alpha-VCAM-1 or alpha-VLA-4 mAb, but not alpha-ICAM-1 or alpha-LFA-1, abrogated the poly-ICLC and IL-2-induced increase in organ-associated NK activity and percentage of tumor-associated NK cells, resulted in a 61 to 76% decrease in pulmonary and hepatic NK cell number, and was independent of T and/or B cells. The decrease in NK cell number in organ parenchyma and tumor lesions was correlated to an increase in the number of NK cells in peripheral blood, but not bone marrow. These results demonstrate that VCAM-1/VLA-4 interaction is critically involved in the infiltration of newly recruited NK cells in to lung, liver, and progressively growing tumor after mobilization from the bone marrow.
Fogler
W E
WE
Laboratory of Experimental Immunology, Division of Basic Sciences, SAIC-Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD 21702-1201, USA.
Volker
K
K
McCormick
K L
KL
Watanabe
M
M
Ortaldo
J R
JR
Wiltrout
R H
RH
D000818:Animals; D002448:Cell Adhesion; D007111:Immunity, Cellular; D039041:Integrin alpha4beta1; D016023:Integrins / Q000502:physiology*; D007694:Killer Cells, Natural / Q000166:cytology*; D008099:Liver / Q000276:immunology; D008168:Lung / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D008546:Melanoma, Experimental / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D011107:Polylysine / Q000494:pharmacology; D016201:Receptors, Lymphocyte Homing / Q000502:physiology*; D012878:Skin Neoplasms / Q000276:immunology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology*
D039041:Integrin alpha4beta1; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D016201:Receptors, Lymphocyte Homing; D019010:Vascular Cell Adhesion Molecule-1; D011107:Polylysine