MilliporeSigma
  • Home
  • Search Results
  • Bisphosphonate-induced differential modulation of immune cell function in gingiva and bone marrow in vivo: role in osteoclast-mediated NK cell activation.

Bisphosphonate-induced differential modulation of immune cell function in gingiva and bone marrow in vivo: role in osteoclast-mediated NK cell activation.

Oncotarget (2015-09-08)
Han-Ching Tseng, Keiichi Kanayama, Kawaljit Kaur, So-Hyun Park, Sil Park, Anna Kozlowska, Shuting Sun, Charles E McKenna, Ichiro Nishimura, Anahid Jewett
ABSTRACT

The aim of this study is to establish osteoclasts as key immune effectors capable of activating the function of Natural Killer (NK) cells, and expanding their numbers, and to determine in vivo and in vitro effect of bisphosphonates (BPs) during NK cell interaction with osteoclasts and on systemic and local immune function. The profiles of 27 cytokines, chemokines and growth factors released from osteoclasts were found to be different from dendritic cells and M1 macrophages but resembling to untreated monocytes and M2 macrophages. Nitrogen-containing BPs Zoledronate (ZOL) and Alendronate (ALN), but not non-nitrogen-containing BPs Etidronate (ETI), triggered increased release of pro-inflammatory mediators from osteoclasts while all three BPs decreased pit formation by osteoclasts. ZOL and ALN mediated significant release of IL-6, TNF-` and IL-1β, whereas they inhibited IL-10 secretion by osteoclasts. Treatment of osteoclasts with ZOL inhibited NK cell mediated cytotoxicity whereas it induced significant secretion of cytokines and chemokines. NK cells lysed osteoclasts much more than their precursor cells monocytes, and this correlated with the decreased expression of MHC class I expression on osteoclasts. Intravenous injection of ZOL in mice induced pro-inflammatory microenvironment in bone marrow and demonstrated significant immune activation. By contrast, tooth extraction wound of gingival tissues exhibited profound immune suppressive microenvironment associated with dysregulated wound healing to the effect of ZOL which could potentially be responsible for the pathogenesis of Osteonecrosis of the Jaw (ONJ). Finally, based on the data obtained in this paper we demonstrate that osteoclasts can be used as targets for the expansion of NK cells with superior function for immunotherapy of cancer.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Propidium iodide, ≥94.0% (HPLC)
Sigma-Aldrich
Luperox® A75, Benzoyl peroxide, 75%, remainder water
Sigma-Aldrich
Ethanol Fixative 80% v/v, suitable for fixing solution (blood films)
Supelco
Ethanol standards 10% (v/v), 10 % (v/v) in H2O, analytical standard
Sigma-Aldrich
Sodium pyruvate, BioXtra, ≥99%
Sigma-Aldrich
Benzoyl peroxide blend with dicyclohexyl phthalate, suitable for use as a catalyst for electron microscopy. Modified to render it safe in transit.
Sigma-Aldrich
Sodium bicarbonate, Hybri-Max, powder, suitable for hybridoma, ≥99.5%
Sigma-Aldrich
Sodium bicarbonate, BioXtra, 99.5-100.5%
Sigma-Aldrich
Sodium bicarbonate, powder, BioReagent, for molecular biology, suitable for cell culture, suitable for insect cell culture
Sigma-Aldrich
Sodium pyruvate, Hybri-Max, powder, suitable for hybridoma
Sigma-Aldrich
Sodium pyruvate, ReagentPlus®, ≥99%
Sigma-Aldrich
Luperox® A75FP, Benzoyl peroxide, 75% remainder water, contains 25 wt. % water as stabilizer, 75%
Sigma-Aldrich
Methyl methacrylate, 99%, stabilized
Sigma-Aldrich
Sodium pyruvate, powder, BioXtra, suitable for mouse embryo cell culture
Sigma-Aldrich
Sodium pyruvate, powder, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥99%
Sigma-Aldrich
Methyl methacrylate, contains ≤30 ppm MEHQ as inhibitor, 99%
Sigma-Aldrich
Luperox® A98, Benzoyl peroxide, reagent grade, ≥98%
Sigma-Aldrich
Luperox® A70S, Benzoyl peroxide, 70%, remainder water
Sigma-Aldrich
Dibutyl phthalate, 99%
Sigma-Aldrich
Luperox® AFR40, Benzoyl peroxide solution, 40 wt. % in dibutyl phthalate
Sigma-Aldrich
Sodium pyruvate, anhydrous, free-flowing, Redi-Dri, ReagentPlus®, ≥99%
Sigma-Aldrich
Ethyl alcohol, Pure, 190 proof, meets USP testing specifications
Sigma-Aldrich
Sodium bicarbonate-12C, 99.9 atom % 12C
Sigma-Aldrich
Ethyl alcohol, Pure, 190 proof, ACS spectrophotometric grade, 95.0%
Sigma-Aldrich
Nitrogen, ≥99.998%
Sigma-Aldrich
Ethyl alcohol, Pure, 200 proof, anhydrous, ≥99.5%
Sigma-Aldrich
L-Glutamine, BioUltra, ≥99.5% (NT)
Sigma-Aldrich
Sodium phosphate dibasic dodecahydrate, BioXtra, ≥99.0% (T)
Sigma-Aldrich
Propidium iodide solution, solution (1.0 mg/ml in water)
SAFC
L-Glutamine