Anti-Asialo GM1 NK Cell Depleting Antibody Does Not Alter the Development of Bleomycin Induced Pulmonary Fibrosis

Monnier, Justin; Zabel, Brian A.

doi:10.1371/journal.pone.0099350

Cited by 21 publications

(12 citation statements)

References 41 publications

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“…For depletion of NK cells, we used a common and validated method . Briefly, rabbit anti‐mouse asialo GM1 (200 μL/1:10 dilution of original stock; Wako Chemicals, Tokyo, Japan was given by tail vein injection every 4 days for five injections starting on day 4 before the beginning of administration of antitumor agents.…”

Section: Methodsmentioning

confidence: 99%

“…For depletion of NK cells, we used a common and validated method. (20) Briefly, rabbit anti-mouse asialo GM1 (200 lL/1:10 dilution of original stock; Wako Chemicals, Tokyo, Japan was given by tail vein injection every 4 days for five injections starting on day 4 before the beginning of administration of antitumor agents. For subsequent detection of infiltrating CD11b-positive cells and NK cells in the tumor, APC-conjugated rat anti-mouse CD11b antibody (Pharmingen BD Biosciences, Tokyo, Japan) or anti-rabbit NCR1 antibody (Abcam, Tokyo, Japan) were used with frozen tissue and paraffin-embedded tissues, respectively.…”

Section: Methodsmentioning

confidence: 99%

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Antitumor effects of eribulin depend on modulation of the tumor microenvironment by vascular remodeling in mouse models

Ito

Hamamichi²,

Abe

et al. 2017

Cancer Science

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We previously reported that eribulin mesylate (eribulin), a tubulin‐binding drug (TBD), could remodel tumor vasculature (i.e. increase tumor vessels and perfusion) in human breast cancer xenograft models. However, the role of this vascular remodeling in antitumor effects is not fully understood. Here, we investigated the effects of eribulin‐induced vascular remodeling on antitumor activities in multiple human cancer xenograft models. Microvessel densities (MVD) were evaluated by immunohistochemistry (CD31 staining), and antitumor effects were examined in 10 human cancer xenograft models. Eribulin significantly increased MVD compared to the controls in six out of 10 models with a correlation between enhanced MVD levels and antitumor effects (R 2 = 0.54). Because of increased MVD, we next used radiolabeled liposomes to examine whether eribulin treatment would result in increased tumoral accumulation levels of these macromolecules and, indeed, we found that eribulin, unlike vinorelbine (another TBD) enhanced them. As eribulin increased accumulation of radiolabeled liposomes, we postulated that this treatment might enhance the antitumor effect of Doxil (a liposomal anticancer agent) and facilitate recruitment of immune cells into the tumor. As expected, eribulin enhanced antitumor activity of Doxil in a post‐erlotinib treatment H1650 (PE‐H1650) xenograft model. Furthermore, infiltrating CD11b‐positive immune cells were significantly increased in multiple eribulin‐treated xenografted tumors, and natural killer (NK) cell depletion reduced the antitumor effects of eribulin. These findings suggest a contribution of the immune cells for antitumor activities of eribulin. Taken together, our results suggest that vascular remodeling induced by eribulin acts as a microenvironment modulator and, consequently, this alteration enhanced the antitumor effects of eribulin.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Antitumor effects of eribulin depend on modulation of the tumor microenvironment by vascular remodeling in mouse models

Ito

Hamamichi²,

Abe

et al. 2017

Cancer Science

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“…NK cells were depleted in a subset of normal pregnant (NP) and RUPP rats by an intraperitoneal injection of 100 μl (3.5 μg) anti-asialo ganglio-N-tetraosylceramide (anti-asialo-GM1) antibodies (Wako Chemicals, Richmond, VA) in water on days 15 and 17 of gestation [26–28]. Asialo-GM1 (ASGM1) is a glycophospolipid expressed on the surface of NK cells that is a target of immune cell response and acts as a coreceptor for pathogens.…”

Section: Methodsmentioning

confidence: 99%

Natural killer cells mediate pathophysiology in response to reduced uterine perfusion pressure

et al. 2017

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Preeclampsia is associated with hypertension, small-for-gestational-age babies, and increased cytolytic natural killer (NK) cells. The specific role of cytolytic NK cells in the pathophysiology of preeclampsia has not been clearly defined. We hypothesized that Reduced Uterine Perfusion Pressure (RUPP) stimulates proliferation and cytolytic activation of NK cells, and that reducing NK cells in RUPP would prevent hypertension, intrauterine growth restriction, and inflammation in response to placental ischemia. RUPP was induced on gestation day (GD) 14 in pregnant rats. NK cells were depleted by i.p. administration of anti-asialo GM1 antibody on GDs 15 and 17. Placental and circulating NK cells were quantified via flow cytometry, mean arterial pressure (MAP), fetal weights, and cytokines were measured on GD 19. Total placental NK cells were 7.4±2% of gated cells in normal pregnant (NP; n=10) and 16.5± 3% of gated cells in RUPP (n=10) rats. Furthermore, cytolytic placental NK cells also increased in RUPP. Depletion of NK cells in RUPP (RUPP + anti-ASGM1) significantly improved MAP and fetal weights. MAP was 108± 2 mmHg in NP, 125± 2 mmHg in RUPP, and 112± 2 mmHg in RUPP + anti-ASGM1 (n=12). Fetal weight was 2.32 ± 0.05 in NP, 1.8± 0.04g in RUPP, and increased to 2.0± 0.04g in RUPP + anti-ASGM1. Placental interferon-γ (IFN-γ) was 40.4± 5.2 pg/mg in NP, 72.17± 3.2 pg/mg in RUPP, and 44.0± 6.5 pg/mg in RUPP + anti-ASGM1 (P<0.05). Placental tumor necrosis factor-α (TNF-α) was 17.9± 1.7 pg/mg in NP, 23.9± 2.2 pg/mg in RUPP, and 12.9± 2.3 pg/mg in RUPP + anti-ASGM1 (P<0.05). Depletion of NK cells significantly lowered MAP, intrauterine growth restriction, and inflammation in RUPP rats indicating that cytolytic NK cells are important in preeclampsia pathophysiology.

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“…C57BL/6J, SJL and NZB), this antibody does not work in other strains of mice due to allelic variation in the NKR-P1 gene that encodes NK1.1 (CD161) (23, 24). In contrast, anti-AsGM1 antibody robustly depletes NK cells across multiple strains of mice including C57BL/6J, BALB/c, DBA2 and 129 strains, and remains in use to this day (22, 25, 26). …”

Section: Introductionmentioning

confidence: 99%

Tissue-Resident NK Cells Mediate Ischemic Kidney Injury and Are Not Depleted by Anti–Asialo-GM1 Antibody

Victorino

Sojka

Brodsky

et al. 2015

The Journal of Immunology

100

104

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NK cells are innate lymphoid cells important for immune surveillance, identifying and responding to stress, infection, and/or transformation. While conventional NK (cNK) cells circulate systemically, many NK cells reside in tissues where they appear to be poised to locally regulate tissue function. Here we tested the contribution of tissue-resident NK (trNK) cells to tissue homeostasis by studying ischemic injury in the mouse kidney. Parabiosis experiments demonstrate that the kidney contains a significant fraction of trNK cells under homeostatic conditions. Kidney trNK cells developed independent of NFIL3 and Tbet, and expressed a distinct cell surface phenotype as compared to cNK cells. Among these, trNK cells had reduced asialo-GM1 (AsGM1) expression relative to cNK cells, a phenotype observed in trNK cells across multiple organs and mouse strains. Strikingly, anti-AsGM1 antibody treatment, commonly used as NK cell-depleting regimen, resulted in a robust and selective depletion of cNKs, leaving trNKs largely intact. Using this differential depletion, we tested the relative contribution of cNK and trNK cells in ischemic kidney injury. Whereas anti-NK1.1 antibody effectively depleted both trNK and cNK cells and protected against ischemic-reperfusion injury, anti-AsGM1 antibody preferentially depleted cNK cells and failed to protect against injury. These data demonstrate unanticipated specificity of anti-AsGM1 antibody depletion on NK cell subsets and reveal a new approach to study the contributions of cNK and trNK cells in vivo. In total, these data demonstrate that trNK cells play a key role in modulating local responses to ischemic tissue injury in the kidney and potentially other organs.

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Anti-Asialo GM1 NK Cell Depleting Antibody Does Not Alter the Development of Bleomycin Induced Pulmonary Fibrosis

Cited by 21 publications

References 41 publications

Antitumor effects of eribulin depend on modulation of the tumor microenvironment by vascular remodeling in mouse models

Antitumor effects of eribulin depend on modulation of the tumor microenvironment by vascular remodeling in mouse models

Natural killer cells mediate pathophysiology in response to reduced uterine perfusion pressure

Tissue-Resident NK Cells Mediate Ischemic Kidney Injury and Are Not Depleted by Anti–Asialo-GM1 Antibody

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