scholarly journals A protocol for macrophage depletion and reconstitution in a mouse model of sepsis

2021 ◽  
Vol 2 (4) ◽  
pp. 101004
Author(s):  
Tivoli Nguyen ◽  
Jie Du ◽  
Yan Chun Li
Keyword(s):  
Mouse Model ◽  
Macrophage Depletion

scholarly journals 873 Pharmacologic macrophage depletion affects metastasis formation by modulating systemic immune responses in a genetic pancreatic cancer model

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A926-A926
Author(s):  
Heidi Griesmann ◽  
Heidi Griesmann ◽  
Heidi Griesmann ◽  
Christof Drexel ◽  
Nada Milosevic ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
T Cells ◽  
Regulatory T Cells ◽  
Mouse Model ◽  
Immune Cells ◽  
Tumour Progression ◽  
Metastasis Formation ◽  
Macrophage Depletion ◽  
Genetic Mouse Model ◽  
Liposomal Clodronate

BackgroundTumour-associated macrophages (TAM) play an important role in mediating tumour progression. In pancreatic cancer, infiltrating macrophages have been identified not only in invasive tumours, but also in early preinvasive pancreatic intraepithelial neoplasias and are known to mediate tumour progression.MethodsWe aimed to study the impact of pharmacological macrophage depletion by liposomal clodronate in the genetic mouse model of pancreatic cancer (KPC mouse: LSL-KrasG12D/+;LSL-Trp53R172H/+;Pdx-1-Cre). KPC mice were treated with liposomal clodronate or control liposomes from week 8 to week 20. Tumour and metastasis formation as well as alterations in local and circulating immune cells and cytokines were analysed.ResultsTreatment with liposomal clodronate effectively reduced CD11b-positive macrophages both in the pancreas and other organs such as liver, lung and spleen. Tumour incidence and size was only slightly reduced. However, metastasis formation in the liver und lungs was markedly diminished after macrophage depletion. Reduced macrophage count was associated with significant alterations in circulating growth factors and mediators known to be secreted by macrophages and associated with angiogenesis, most prominently VEGF. Moreover, application of liposomal clodronate led to marked alterations in circulating immune cells, among them reduced regulatory T cells.ConclusionsPharmacological depletion of macrophages in a genetic mouse model of pancreatic cancer markedly reduced metastasis formation and is associated with modulated profile of both secreted mediators and regulatory T cells. Pharmacological modulation of infiltrating macrophages represents a promising avenue for antimetastatic therapeutic approaches.

scholarly journals Treatment of arthritis by macrophage depletion and immunomodulation: Testing an apoptosis-mediated therapy in a humanized death receptor mouse model

2012 ◽  
Vol 64 (4) ◽  
pp. 1098-1109 ◽  
Author(s):  
Jun Li ◽  
Hui-Chen Hsu ◽  
PingAr Yang ◽  
Qi Wu ◽  
Hao Li ◽  
...  
Keyword(s):  
Mouse Model ◽  
Death Receptor ◽  
Macrophage Depletion

scholarly journals Adenovirus-Mediated Inducible Expression of a PD-L1 Blocking Antibody in Combination with Macrophage Depletion Improves Survival in a Mouse Model of Peritoneal Carcinomatosis

2021 ◽  
Vol 22 (8) ◽  
pp. 4176
Author(s):  
Maria Buñuales ◽  
Maria Cristina Ballesteros-Briones ◽  
Manuela Gonzalez-Aparicio ◽  
Sandra Hervas-Stubbs ◽  
Eva Martisova ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mouse Model ◽  
Peritoneal Carcinomatosis ◽  
Checkpoint Inhibitors ◽  
High Capacity ◽  
Systemic Exposure ◽  
Blocking Antibody ◽  
Macrophage Depletion ◽  
Polycytidylic Acid ◽  
Gene Therapy Vectors

Immune checkpoint inhibitors (ICIs) have demonstrated remarkable efficacy in a growing number of malignancies. However, overcoming primary or secondary resistances is difficult due to pharmacokinetics issues and side effects associated with high systemic exposure. Local or regional expression of monoclonal antibodies (mAbs) using gene therapy vectors can alleviate this problem. In this work, we describe a high-capacity adenoviral vector (HCA-EFZP-aPDL1) equipped with a mifepristone-inducible system for the controlled expression of an anti-programmed death ligand 1 (PD-L1) blocking antibody. The vector was tested in an immune-competent mouse model of colorectal cancer based on implantation of MC38 cells. A single local administration of HCA-EFZP-aPDL1 in subcutaneous lesions led to a significant reduction in tumor growth with minimal release of the antibody in the circulation. When the vector was tested in a more stringent setting (rapidly progressing peritoneal carcinomatosis), the antitumor effect was marginal even in combination with other immune-stimulatory agents such as polyinosinic-polycytidylic acid (pI:C), blocking mAbs for T cell immunoglobulin, mucin-domain containing-3 (TIM-3) or agonistic mAbs for 4-1BB (CD137). In contrast, macrophage depletion by clodronate liposomes enhanced the efficacy of HCA-EFZP-aPDL1. These results highlight the importance of addressing macrophage-associated immunoregulatory mechanisms to overcome resistance to ICIs in the context of colorectal cancer.

scholarly journals Macrophages inhibit and enhance endometriosis depending on their origin

2021 ◽  
Vol 118 (6) ◽  
pp. e2013776118 ◽  
Author(s):  
Chloe Hogg ◽  
Kavita Panir ◽  
Priya Dhami ◽  
Matthew Rosser ◽  
Matthias Mack ◽  
...  
Keyword(s):  
Mouse Model ◽  
Disease Progression ◽  
Peritoneal Macrophage ◽  
Peritoneal Macrophages ◽  
Inflammatory Disorder ◽  
Chronic Inflammatory Disorder ◽  
Macrophage Depletion ◽  
Monocyte Recruitment ◽  
Macrophage Populations ◽  
And Function

Macrophages are intimately involved in the pathophysiology of endometriosis, a chronic inflammatory disorder characterized by the growth of endometrial-like tissue (lesions) outside the uterus. By combining genetic and pharmacological monocyte and macrophage depletion strategies we determined the ontogeny and function of macrophages in a mouse model of induced endometriosis. We demonstrate that lesion-resident macrophages are derived from eutopic endometrial tissue, infiltrating large peritoneal macrophages (LpM) and monocytes. Furthermore, we found endometriosis to trigger continuous recruitment of monocytes and expansion of CCR2+ LpM. Depletion of eutopic endometrial macrophages results in smaller endometriosis lesions, whereas constitutive inhibition of monocyte recruitment significantly reduces peritoneal macrophage populations and increases the number of lesions. Reprogramming the ontogeny of peritoneal macrophages such that embryo-derived LpM are replaced by monocyte-derived LpM decreases the number of lesions that develop. We propose a putative model whereby endometrial macrophages are “proendometriosis” while newly recruited monocyte-derived macrophages, possibly in LpM form, are “antiendometriosis.” These observations highlight the importance of monocyte-derived macrophages in limiting disease progression.

scholarly journals Macrophage Depletion Attenuates Extracellular Matrix Deposition and Ductular Reaction in a Mouse Model of Chronic Cholangiopathies

PLoS ONE ◽  
2016 ◽  
Vol 11 (9) ◽  
pp. e0162286 ◽  
Author(s):  
Jan Best ◽  
Stefaan Verhulst ◽  
Wing-Kin Syn ◽  
Kimberly Lagaisse ◽  
Noemi van Hul ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Mouse Model ◽  
Ductular Reaction ◽  
Matrix Deposition ◽  
Macrophage Depletion ◽  
Extracellular Matrix Deposition

Macrophage depletion diminishes implant-wear-induced inflammatory osteolysis in a mouse model

2008 ◽  
Vol 85A (4) ◽  
pp. 1043-1051 ◽  
Author(s):  
Weiping Ren ◽  
David C. Markel ◽  
Reto Schwendener ◽  
Yunhong Ding ◽  
Bin Wu ◽  
...  
Keyword(s):  
Mouse Model ◽  
Macrophage Depletion ◽  
Implant Wear

scholarly journals A Transgenic Mouse Model of Inducible Macrophage Depletion

2009 ◽  
Vol 175 (1) ◽  
pp. 132-147 ◽  
Author(s):  
Itamar Goren ◽  
Nadine Allmann ◽  
Nir Yogev ◽  
Christoph Schürmann ◽  
Andreas Linke ◽  
...  
Keyword(s):  
Mouse Model ◽  
Transgenic Mouse ◽  
Transgenic Mouse Model ◽  
Macrophage Depletion

scholarly journals Modifying Graft-versus-Host Disease in a Humanized Mouse Model by Targeting Macrophages or B-Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Marieke C. H. Hogenes ◽  
Suzanne van Dorp ◽  
Joyce van Kuik ◽  
Filipa R. P. Monteiro ◽  
Natalie ter Hoeve ◽  
...  
Keyword(s):  
B Cells ◽  
Mouse Model ◽  
B Cell ◽  
Cell Depletion ◽  
Mrna Levels ◽  
B Cell Depletion ◽  
Humanized Mouse ◽  
Humanized Mouse Model ◽  
Graft Versus Host ◽  
Macrophage Depletion

Humanized mouse models can well be modified to study specific aspects of Graft-versus-Host Disease (GvHD). This paper shows the results of both macrophage depletion and (early) B-cell depletion in a humanized mouse model using RAG2-/-γc-/- mice injected with HuPBMCs. Macrophage depletion showed a significant decrease in survival and also lead to a change in the histomorphology of the xenogeneic reaction. Higher levels of infiltrating B-cells were observed in various organs of mice depleted for macrophages. With (early) B-cell depletion using Rituximab, a clear improvement on clinical symptoms was observed, even when probably only inactivated B-cells were deleted. However, the histological examinations only showed a significant morphological effect on liver fibrosis. This may be related to a difference in the mRNA levels of TGF-β. Also, lower mRNA levels of Tregs in some organs were observed after Rituximab treatment, which contradicts that a higher number of Tregs would always be related to less severe GvHD. Our data show that both macrophage depletion and (early) B-cell depletion in a xenogeneic mouse model can influence the clinical, histological, and cytokine production of a GvHD response.

scholarly journals Macrophages inhibit and enhance endometriosis depending on their origin

2020 ◽  
Author(s):  
Chloe Hogg ◽  
Priya Dhami ◽  
Matthew Rosser ◽  
Matthias Mack ◽  
Daniel Soong ◽  
...  
Keyword(s):  
Mouse Model ◽  
Disease Progression ◽  
Peritoneal Macrophage ◽  
Peritoneal Macrophages ◽  
Inflammatory Disorder ◽  
Chronic Inflammatory Disorder ◽  
Macrophage Depletion ◽  
Monocyte Recruitment ◽  
Macrophage Populations ◽  
And Function

AbstractMacrophages are intimately involved in the pathophysiology of endometriosis, a chronic inflammatory disorder characterized by the growth of endometrial-like tissue (lesions) outside the uterus. By combining genetic and pharmacological monocyte and macrophage depletion strategies we determined the ontogeny and function of macrophages in a mouse model of induced endometriosis. We demonstrate that lesion-resident macrophages are derived from eutopic endometrial tissue, infiltrating large peritoneal macrophages (LpM) and monocytes. Furthermore, we found endometriosis to trigger continuous recruitment of monocytes and expansion of CCR2+ LpM. Depletion of eutopic endometrial macrophages results in smaller endometriosis lesions, whereas constitutive inhibition of monocyte recruitment significantly reduces peritoneal macrophage populations and increased the number of lesions. We propose a putative model whereby endometrial macrophages are pro-endometriosis whilst newly-recruited monocyte-derived macrophages, possibly in LpM form, are ‘anti-endometriosis’. These observations highlight the importance of monocyte-derived macrophages in limiting disease progression.

Sign in / Sign up

Export Citation Format

Share Document