title: The marginating-pulmonary immune compartment in mice exhibits increased NK cytotoxicity and unique cellular characteristics.
abstract: To test whether marginating-pulmonary (MP) leukocytes in mice have a unique potential to identify and destroy aberrant circulating cells, we compared MP to circulating leukocytes with respect to natural killer (NK) cytotoxicity, proinflammatory characteristics, molecular determinants of activation, and response to IL-12 immunostimulation. Cytotoxicity was assessed employing the YAC-1, B16F10, and 3LL target lines. C57BL/6 mice were injected with either saline or murine IL-12 (0.1 or 0.5 µg/mouse), either once or three times 48-h apart. Twenty-four hours after last injection, cardiac blood was withdrawn and MP leukocytes were collected by forced lung perfusion. NK cytotoxicity, cellular composition, and surface molecular markers were studied. MP leukocytes exhibited greater NK cytotoxicity than circulating leukocytes against the syngeneic B16F10 and 3LL tumor lines, but not against the allogeneic YAC-1 line. NKG2D and IL-12 receptor expression predicted NK cytotoxicity in circulating leukocytes, but not in MP leukocytes. IFNγ-receptor, IL-12-receptor, CD69, CD11a, and CD11b showed different patterns of expression in the two leukocyte populations, suggesting pro-inflammatory characteristics of the MP compartment. IL-12 stimulation caused differential effects on these markers and also elevated cytotoxicity in both compartments, but in different effector: target ratio-dependent patterns. MP leukocytes may play a critical role in eliminating aberrant circulating cells due to their enhanced NK cytotoxicity and given their strategic location in the lungs vasculature, which forces physical interactions with all circulating aberrant cells. MP-NK cells are unique in their cytotoxic mechanisms against syngeneic targets and in their activation profile and response to immunostimulatory agents.
authors.affiliation: Neuroimmunology Research Unit, The Sagol School of Neuroscience, The School of Psychological Sciences, Tel Aviv University, Room #113b, Sharett Building, Tel Aviv, 69978, Israel, benishd@post.tau.ac.il.
authors.forename: Marganit
authors.initials: M
authors.lastname: Benish
authors.forename: Rivka
authors.initials: R
authors.lastname: Melamed
authors.forename: Ella
authors.initials: E
authors.lastname: Rosenne
authors.forename: Elad
authors.initials: E
authors.lastname: Neeman
authors.forename: Liat
authors.initials: L
authors.lastname: Sorski
authors.forename: Ben
authors.initials: B
authors.lastname: Levi
authors.forename: Lee
authors.initials: L
authors.lastname: Shaashua
authors.forename: Pini
authors.initials: P
authors.lastname: Matzner
authors.forename: Shamgar
authors.initials: S
authors.lastname: Ben-Eliyahu
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D040881:CD11a Antigen / Q000276:immunology; D039481:CD11b Antigen / Q000276:immunology; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D005260:Female; D005434:Flow Cytometry; D018664:Interleukin-12 / Q000276:immunology*; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D037181:Lectins, C-Type / Q000276:immunology; D007962:Leukocytes / Q000166:cytology / Q000276:immunology*; D008168:Lung / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017471:Receptors, Interferon / Q000276:immunology; D053707:Receptors, Interleukin-12 / Q000276:immunology; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D040881:CD11a Antigen; D039481:CD11b Antigen; D018664:Interleukin-12; D037181:Lectins, C-Type; D017471:Receptors, Interferon; D053707:Receptors, Interleukin-12; D000099192:CD69 Antigens