The marginating-pulmonary immune compartment in mice exhibits increased NK cytotoxicity and unique cellular characteristics

Marganit Benish*, Rivka Melamed, Ella Rosenne, Elad Neeman, Liat Sorski, Ben Levi, Lee Shaashua, Pini Matzner, Shamgar Ben-Eliyahu

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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 Twenty-four hours after last injection, cardiac blood was withdrawn and MP leukocytes were collected by forced lung perfusion.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.

Original languageEnglish
Pages (from-to)28-39
Number of pages12
JournalImmunologic Research
Volume58
Issue number1
DOIs
StatePublished - Jan 2014

Funding

FundersFunder number
Israel-USA bi-national Science Foundation2005331
National Institute of HealthCA125456
National Cancer InstituteR01CA172138

    Keywords

    • Cell surface markers
    • Inflammation
    • Marginating-pulmonary
    • NK cytotoxicity

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