Megakaryocytes as immune cells

Cunin, Pierre; Nigrović, Peter A.

doi:10.1002/jlb.mr0718-261rr

Cited by 66 publications

(71 citation statements)

References 121 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Megakaryocytes might also play a direct role in the pathogenesis of ITP. Platelets have long been recognized as immune cells with the ability to promote leukocyte and endothelial activation, stimulate neutrophil extracellular trap formation, detect and clear pathogens, and promote inflammation . However, the concept of megakaryocytes as immune cells is just starting to emerge .…”

Section: Itp Nomenclature and Pathogenesis Updatementioning

confidence: 99%

“…Platelets have long been recognized as immune cells with the ability to promote leukocyte and endothelial activation, stimulate neutrophil extracellular trap formation, detect and clear pathogens, and promote inflammation . However, the concept of megakaryocytes as immune cells is just starting to emerge . Megakaryocytes express immune‐sensing receptors, like TLRs and IgG Fc receptors, and they can modulate other bone marrow hematopoietic cells via release of mediators .…”

Section: Itp Nomenclature and Pathogenesis Updatementioning

confidence: 99%

“…However, the concept of megakaryocytes as immune cells is just starting to emerge . Megakaryocytes express immune‐sensing receptors, like TLRs and IgG Fc receptors, and they can modulate other bone marrow hematopoietic cells via release of mediators . Megakaryocytes can stimulate Th17 expansion and also promote inflammation by the release of IL‐1 rich microparticles .…”

Section: Itp Nomenclature and Pathogenesis Updatementioning

confidence: 99%

See 2 more Smart Citations

Immune thrombocytopenia (ITP): Pathophysiology update and diagnostic dilemmas

LeVine

Brooks

2019

Veterinary Clinical Pathol

View full text Add to dashboard Cite

Immune thrombocytopenia (ITP) is a common autoimmune bleeding disorder. The understanding of ITP pathogenesis is rapidly evolving. We now recognize ITP as a complex and heterogeneous syndrome that results from a combination of humoral and cell-mediated attacks on platelets peripherally and megakaryocytes in the bone marrow. Autoantibody-mediated ITP also varies in the pathway used to clear platelets, which depends on the platelet glycoprotein being targeted. Moreover, ITP patients present with variable bleeding severities and treatment responses that do not closely correlate with platelet count. A gold standard diagnostic test for ITP is lacking, and biomarkers to assess disease severity are in their infancy. This review provides an update on the immunopathogenesis of ITP and summarizes currently available tests for ITP diagnosis, prediction of disease severity, and treatment responses. Given the heterogeneous pathogenesis and clinical presentation of ITP, we highlight the need for the development of diagnostic and prognostic tests that would allow for the individualized management of a complex disease. K E Y W O R D Sautoantibodies/autoimmune disease, bleeding score, dog, hemorrhage, immune thrombocytopenia, immunology, platelet

show abstract

Section: Itp Nomenclature and Pathogenesis Updatementioning

confidence: 99%

Section: Itp Nomenclature and Pathogenesis Updatementioning

confidence: 99%

Section: Itp Nomenclature and Pathogenesis Updatementioning

confidence: 99%

See 1 more Smart Citation

Immune thrombocytopenia (ITP): Pathophysiology update and diagnostic dilemmas

LeVine

Brooks

2019

Veterinary Clinical Pathol

View full text Add to dashboard Cite

show abstract

mentioning

confidence: 99%

“…The participation of MKs in immune responses is suggested by several anecdotal observations 19 . Maturing MKs express both major histocompatibility complex (MHC) class I and II molecules and a variety of toll-like receptors (TLRs) on their cell surface 13–19 . MKs, just like platelets, also contain various granule types, including lysosomes, which participate in the endocytosis and degradation of pathogens 20 .…”

mentioning

confidence: 99%

Megakaryocytes Display Innate Immune Cell Functions and Respond during Sepsis

Frydman

Ellett

Jorgensen

et al. 2019

Preprint

View full text Add to dashboard Cite

24 Megakaryocytes (MKs) are precursors to platelets, the second most abundant cells in the 25 peripheral circulation. However, while platelets are known participate in immune responses and 26 play significant roles during infections, the role of MKs within the immune system has not been 27 explored. Here we utilize in vitro techniques to show that both cord blood-derived MKs (CB 28 MKs) and MKs from a human megakaryoblastic leukemia cell line (Meg-01) chemotax towards 29 pathogenic stimuli, phagocytose bacteria, and release chromatin webs in response to bacteria.30 Moreover, in patients with sepsis, we found that MK counts were significantly higher in the 31 peripheral blood, and CD61 + staining was increased in the kidneys and lungs, correlated with the 32 development of organ dysfunction. Overall, our study suggests that MK cells display basic innate 33 immune cell functions and respond during infections and sepsis.3 34 Megakaryocytes (MKs) are commonly recognized as key participants in hemostatic processes 35 through the production of platelets 1-2 . In addition to their presence in the bone marrow, MKs can 36 also be located in the lungs, lymph nodes, spleen, and liver during extra medullary hematopoiesis 3-37 7 . MKs have also been reported to be significantly increased in the lungs during severe pulmonary 38 inflammation, such as acute respiratory distress syndrome (ARDS), when they are believed to 39 promote inflammation via the release of platelets [8][9][10] . The current paradigm by which MKs are 40 increased in the lungs during ARDS revolves around MKs passive escape from the bone marrow, 41 entrance to arterial circulation, and passive mechanical entrapment within the microcirculatory bed 42 of the alveoli 4,11-12 . 4344 The participation of MKs in immune responses is suggested by several anecdotal observations 19 .45 Maturing MKs express both major histocompatibility complex (MHC) class I and II molecules 46 and a variety of toll-like receptors (TLRs) on their cell surface [13][14][15][16][17][18][19] . MKs, just like platelets, also 47 contain various granule types, including lysosomes, which participate in the endocytosis and 48 degradation of pathogens 20 . MKs can play antigen-presenting-cell (APC) roles and stimulate Th-49 17 responses in lupus 13,21 . Thrombocytes, the amphibian equivalent of the mammalian 50 MK/platelet, actively phagocytose live bacteria [23][24][25] . In mammals, MKs internalize viruses, 51 including dengue virus and HIV, and multiple case reports show evidence for MKs containing 52 fungi [26][27][28][29] . Although such reports provide sporadic support for an active role for MKs in the 53 immune responses, this function of MKs has not been tested systematically. 5455 Here, we show that the human MKs can engulf pathogens, release chromatin nets, and undergo 56 chemotaxis in gradients of standard chemoattractants. Moreover, we find that during sepsis, the 4 57 number of large CD61 + CD41 + cells increases in peripheral circulation, and the number of large 58 CD61 + cells in...

show abstract

Nano‐Mediated PDT as a Multifunctional Immunomodulatory Agent in the Intricate Milieu of Melanoma

Sebak,

Abdel‐Halim,

Abdelrahman

et al. 2024

Advanced Therapeutics

View full text Add to dashboard Cite

The complexity of the tumor microenvironment (TME) and nutrient competition represent the main causes of therapy resistance in cancers, including malignant melanoma (MM). Photodynamic therapy (PDT), through a cascade of events including its ability to induce significant immune responses, causes tumor eradication. However, the high pigmentation level of melanoma, lack of adequate accumulation of photosensitizers (PSs) in the target tissue as well as their nonspecific toxicity represent three main obstacles to obtaining satisfactory responses in melanoma. To prevail over these challenges, this study employed a depigmentation strategy followed by a nano‐mediated topical application of PDT using a chlorophyllin derivative as PS, focusing on evaluation of the immunomodulatory and metabolic regulatory axes of PDT in melanoma. Photo‐immunomodulation was assessed in a melanoma mouse model using a nanocarrier system of the PS. Markers of the immunosuppressive microenvironment and T cell exhaustion, as independent immune hallmarks, were quantified. The histopathology of spleen and skin/tumor was evaluated. The amino acid profile was quantified from normal skin or tumor biopsies using UHPLC‐MS/MS. Around 80% of the 300 nm transethosomal ferrous chlorophyllin (fC‐TEs) were retained in the tumor over 24 h upon topical application. Arbutin 2% gel not only decreased the melanin content of tumors, but also regulated the expression of interleukin 12 (IL‐12), IL‐10, transforming growth factor beta (TGF‐β) and tumor necrosis factor alpha (TNF‐α). Additionally, the nano‐mediated PDT strategy decreased the expression of programmed cell death protein 1 (PD‐1) & its ligand 1 (PD‐L1) and reduced the activity of arginase 1 (Arg1) through an upregulation of miRNA155. A mild recruitment of megakaryocytes (MKs) was observed in the spleen of the PDT group. This special localization of MKs depicts effector immune properties. Lastly, the combination of PDT and arbutin restored the normal tissue levels of arginine (Arg), glutamine (Gln) and lavished those of tryptophan (Trp). Nano‐mediated PDT represents a novel immunotherapeutic approach in melanoma by a triple modulation of the immune suppressive TME, immune checkpoint signaling, and reprogrammed tumor metabolism.This article is protected by copyright. All rights reserved

show abstract

Megakaryocytes as immune cells

Cited by 66 publications

References 121 publications

Immune thrombocytopenia (ITP): Pathophysiology update and diagnostic dilemmas

Immune thrombocytopenia (ITP): Pathophysiology update and diagnostic dilemmas

Megakaryocytes Display Innate Immune Cell Functions and Respond during Sepsis

Nano‐Mediated PDT as a Multifunctional Immunomodulatory Agent in the Intricate Milieu of Melanoma

Contact Info

Product

Resources

About