Lactotransferrin-Cre reporter mice trace neutrophils, monocytes/macrophages and distinct subtypes of dendritic cells

Kovacic, Boris; Hoelbl-Kovacic, Andrea; Fischhuber, Katrin; Leitner, Nicole R.; Gotthardt, Dagmar; Casanova, Emilio; Sexl, Veronika; Müller, Mathias

doi:10.3324/haematol.2013.097154

Cited by 16 publications

(14 citation statements)

References 38 publications

(60 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…MPO, LF, and elastase are known to be expressed at high levels by neutrophils, but literature suggests that they are also expressed at low levels in monocytes [25][26][27][28]. We confirmed these data on monocytes (Supplemental Fig.…”

Section: Activated Monocytes But Not Modcs Release Net-like Extracellsupporting

confidence: 86%

Human blood monocytes are able to form extracellular traps

Granger

Faille

Marani

et al. 2017

Journal of Leukocyte Biology

115

100

View full text Add to dashboard Cite

Neutrophil extracellular traps (NETs) are extracellular DNA filaments formed during neutrophil activation. This process, called netosis, was originally associated with neutrophil antibacterial properties. However, several lines of evidence now suggest a major role for netosis in thrombosis, autoimmune diseases, and cancer. We demonstrate here that highly purified human blood monocytes are also capable of extracellular trap (ET) release in response to several stimuli. Monocyte ETs display a morphology analogous to NETs and are associated with myeloperoxidase (MPO), lactoferrin (LF), citrullinated histones, and elastase. Monocyte ET release depends on oxidative burst but not on MPO activity, in contrast to neutrophils. Moreover, we demonstrate procoagulant activity for monocyte ETs, a feature that could be relevant to monocyte thrombogenic properties. This new cellular mechanism is likely to have implications in the multiple pathologic contexts where monocytes are implicated, such as inflammatory disorders, infection, or thrombosis.

show abstract

Section: Activated Monocytes But Not Modcs Release Net-like Extracellsupporting

confidence: 86%

Human blood monocytes are able to form extracellular traps

Granger

Faille

Marani

et al. 2017

Journal of Leukocyte Biology

115

100

View full text Add to dashboard Cite

show abstract

“…Literature searches indicated that 14 of the top 25 proteins overexpressed in Pten ‐KO mouse prostate were associated with inflammation and/or immunity. Specifically, myeloid/neutrophil‐related innate immunity marker S100a8/calprotectin and Ltf/lactotransferrin (another myeloid lineage marker tracking neutrophils, monocytes/macrophages, and distinct subtypes of dendritic cells 17 ) stood out along with Reg3g, Pglyrp1, Lgals3, Pigr, Lcn2, Anxa1, Anxa3, and so forth. Other changes included glutathione conjugative metabolism (Gsto1 and Gsta4), proteases related to invasiveness, histones, and chromatin features related to enhanced cell proliferation.…”

Section: Resultsmentioning

confidence: 99%

Proteomic and transcriptomic profiling of Pten gene‐knockout mouse model of prostate cancer

Zhang

Kim

et al. 2020

The Prostate

View full text Add to dashboard Cite

Background The prostate‐specific phosphatase and tensin homolog deleted on chromosome 10 (Pten) gene‐conditional knockout (KO) mouse carcinogenesis model is highly desirable for studies of prostate cancer biology and chemoprevention due to its close resemblance of primary molecular defect and many histopathological features of human prostate cancer including androgen response and disease progression from prostatic intraepithelial neoplasia to invasive adenocarcinoma. Here, we profiled the proteome and transcriptome of the Pten‐KO mouse prostate tumors for global macromolecular expression alterations for signaling changes and biomarker signatures. Methods For proteomics, four pairs of whole prostates from tissue‐specific conditional knockout Pten‐KO mice (12‐15 weeks of age) and their respective wild‐type littermates housed in the same cages were analyzed by 8‐plex isobaric tags for relative and absolute quantitation iTRAQ. For microarray transcriptomic analysis, three additional matched pairs of prostate/tumor specimens from respective mice at 20 to 22 weeks of age were used. Real‐time quantitative reverse transcription‐polymerase chain reaction was used to verify the trends of protein and RNA expression changes. Gene Set Enrichment Analysis and Ingenuity Pathway Analysis were carried out for bioinformatic characterizations of pathways and networks. Results At the macromolecular level, proteomic and transcriptomic analyses complement and cross‐validate to reveal overexpression signatures including inflammation and immune alterations, in particular, neutrophil/myeloid lineage suppressor cell features, chromatin/histones, ion and nutrient transporters, and select glutathione peroxidases and transferases in Pten‐KO prostate tumors. Suppressed expression patterns in the Pten‐KO prostate tumors included glandular differentiation such as secretory proteins and androgen receptor targets, smooth muscle features, and endoplasmic reticulum stress proteins. Bioinformatic analyses identified immune and inflammation responses as the most profound macromolecular landscape changes, and the predicted key nodal activities through Akt, nuclear factor‐kappaB, and P53 in the Pten‐KO prostate tumor. Comparison with other genetically modified mouse prostate carcinogenesis models revealed notable molecular distinctions, especially the dominance of immune and inflammation features in the Pten‐KO prostate tumors. Conclusions Our work identified prominent macromolecular signatures and key nodal molecules that help to illuminate the patho‐ and immunobiology of Pten‐loss driven prostate cancer and can facilitate the choice of biomarkers for chemoprevention and interception studies in this clinically relevant mouse prostate cancer model.

show abstract

“…Similarly, mice expressing cre recombinase together with a diphtheria toxin or its receptor have been developed in order to trace or conditionally delete cells of a target lineage73. Gene loci encoding S100A8 7475, Lyz2 7677, Ltf 78, Elane 79, and Ly6g 80 have been used for targeting neutrophils, although some other types of myeloid cells are labeled to a certain degree. For example, monocytes and macrophages are also labeled in Lyz2 ( LysM ) -cre mice.…”

Section: Resultsmentioning

confidence: 99%

A late-lineage murine neutrophil precursor population exhibits dynamic changes during demand-adapted granulopoiesis

Kim

Yang

Kim

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Homeostasis of neutrophils—the blood cells that respond first to infection and tissue injury—is critical for the regulation of immune responses and regulated through granulopoiesis, a multi-stage process by which neutrophils differentiate from hematopoietic stem cells. Granulopoiesis is a highly dynamic process and altered in certain clinical conditions, such as pathologic and iatrogenic neutropenia, described as demand-adapted granulopoiesis. The regulation of granulopoiesis under stress is not completely understood because studies of granulopoiesis dynamics have been hampered by technical limitations in defining neutrophil precursors. Here, we define a population of neutrophil precursor cells in the bone marrow with unprecedented purity, characterized by the lineage−CD11b+Ly6GloLy6BintCD115−, which we call NeuPs (Neutrophil Precursors). We demonstrated that NeuPs differentiate into mature and functional neutrophils both in vitro and in vivo. By analyzing the gene expression profiles of NeuPs, we also identified NeuP stage-specific genes and characterized patterns of gene regulation throughout granulopoiesis. Importantly, we found that NeuPs have the potential to proliferate, but the proliferation decreased in multiple different hematopoietic stress settings, indicating that proliferating NeuPs are poised at a critical step to regulate granulopoiesis. Our findings will facilitate understanding how the hematopoietic system maintains homeostasis and copes with the demands of granulopoiesis.

show abstract

Lactotransferrin-Cre reporter mice trace neutrophils, monocytes/macrophages and distinct subtypes of dendritic cells

Cited by 16 publications

References 38 publications

Human blood monocytes are able to form extracellular traps

Human blood monocytes are able to form extracellular traps

Proteomic and transcriptomic profiling of Pten gene‐knockout mouse model of prostate cancer

A late-lineage murine neutrophil precursor population exhibits dynamic changes during demand-adapted granulopoiesis

Contact Info

Product

Resources

About