Monocytosis: A new observation during radiotherapy

Rotman, Marvin; Ansley, Hudson R.; Rogow, Louis; Stowe, Stephen P.

doi:10.1016/0360-3016(77)90016-5

Cited by 17 publications

(4 citation statements)

References 12 publications

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“…In addition to increased eosinophils, we also showed an elevated expression of Il6 in the blood of HIR mice, which has previously been observed in human blood samples taken from asthmatic patients, with authors suggesting Il6 to be constitutively synthesised and stored within eosinophils [28, 29]. Isolated studies have also reported eosinophilia secondary to irradiation [30, 31], which typically orchestrates a T cell response to cancer and indirectly stimulates Il6 [32]. Tnfa , another cytokine of pro-inflammation, is typically reduced in the GBM microenvironment.…”

Section: Discussionsupporting

confidence: 79%

Non-myeloablative busulfan chimeric mouse models are less pro-inflammatory than head-shielded irradiation for studying immune cell interactions in brain tumours

Youshani

Rowlston

O’Leary

et al. 2019

J Neuroinflammation

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BackgroundChimeric mouse models generated via adoptive bone marrow transfer are the foundation for immune cell tracking in neuroinflammation. Chimeras that exhibit low chimerism levels, blood-brain barrier disruption and pro-inflammatory effects prior to the progression of the pathological phenotype, make it difficult to distinguish the role of immune cells in neuroinflammatory conditions. Head-shielded irradiation overcomes many of the issues described and replaces the recipient bone marrow system with donor haematopoietic cells expressing a reporter gene or different pan-leukocyte antigen, whilst leaving the blood-brain barrier intact. However, our previous work with full body irradiation suggests that this may generate a pro-inflammatory peripheral environment which could impact on the brain’s immune microenvironment. Our aim was to compare non-myeloablative busulfan conditioning against head-shielded irradiation bone marrow chimeras prior to implantation of glioblastoma, a malignant brain tumour with a pro-inflammatory phenotype.MethodsRecipient wild-type/CD45.1 mice received non-myeloablative busulfan conditioning (25 mg/kg), full intensity head-shielded irradiation, full intensity busulfan conditioning (125 mg/kg) prior to transplant with whole bone marrow from CD45.2 donors and were compared against untransplanted controls. Half the mice from each group were orthotopically implanted with syngeneic GL-261 glioblastoma cells. We assessed peripheral blood, bone marrow and spleen chimerism, multi-organ pro-inflammatory cytokine profiles at 12 weeks and brain chimerism and immune cell infiltration by whole brain flow cytometry before and after implantation of glioblastoma at 12 and 14 weeks respectively.ResultsBoth non-myeloablative conditioning and head-shielded irradiation achieve equivalent blood and spleen chimerism of approximately 80%, although bone marrow engraftment is higher in the head-shielded irradiation group and highest in the fully conditioned group. Head-shielded irradiation stimulated pro-inflammatory cytokines in the blood and spleen but not in the brain, suggesting a systemic response to irradiation, whilst non-myeloablative conditioning showed no cytokine elevation. Non-myeloablative conditioning achieved higher donor chimerism in the brain after glioblastoma implantation than head-shielded irradiation with an altered immune cell profile.ConclusionOur data suggest that non-myeloablative conditioning generates a more homeostatic peripheral inflammatory environment than head-shielded irradiation to allow a more consistent evaluation of immune cells in glioblastoma and can be used to investigate the roles of peripheral immune cells and bone marrow-derived subsets in other neurological diseases.Electronic supplementary materialThe online version of this article (10.1186/s12974-019-1410-y) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 79%

Non-myeloablative busulfan chimeric mouse models are less pro-inflammatory than head-shielded irradiation for studying immune cell interactions in brain tumours

Youshani

Rowlston

O’Leary

et al. 2019

J Neuroinflammation

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“…Taken together, it is conceivable that aging-related clonal haematopoiesis is somehow accelerated by radiation exposure, possibly through cell killing and/or somatic mutations in DNMT3A, TET2, etc., in HSCs, resulting in a life-long monocyte increase among atomic-bomb survivors. Although the follow-up period and the number of participants were quite different from our study, Rotman et al (1977) showed, over 40 years ago, an increase in circulating monocytes at 3 weeks after radiotherapy and discussed an indirect effect of radiation on the bone marrow because they observed no difference in monocyte increase between irradiated regions (pelvic vs thorax: there is twice as much marrow in the pelvic region). HSCs and niche cells in the bone marrow as well as circulating monocytes express receptors, such as Toll-like receptor 4, that are triggered by danger signals from damaged tissues or metabolic abnormality to induce HSC proliferation and myeloid differentiation (Dutta & Nahrendorf, 2014;Murphy et al, 2014;Nahrendorf, 2018).…”

Section: <0001contrasting

confidence: 88%

Radiation exposure and longitudinal changes in peripheral monocytes over 50 years: the Adult Health Study of atomic‐bomb survivors

et al. 2019

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Summary Enhanced inflammatory responses have been suggested decades after radiation exposure in atomic‐bomb survivors, but cellular and molecular alterations related to prolonged inflammation remain unclear. This study, utilizing longitudinal haematological data over 50 years for 14 000 persons, investigated whether radiation exposure promoted the relative increase in peripheral myeloid cells, known as an aging‐associated indicator of low‐grade inflammation. Statistical modelling was performed with a linear mixed‐effects model for leucocyte subsets, together with a proportional hazards regression model for all‐cause mortality. We found that age trends in lymphocyte, neutrophil and monocyte percentages or counts differed before versus after age 60 years. Radiation dose was associated with monocyte percentages and counts, but not with the lymphoid‐myeloid cell ratio. Radiation effects on monocytes were stronger after versus before age 60 years. Increases in monocyte percentages and counts were associated with higher risk of all‐cause mortality. Studies of chromosomal aberrations have shown a clonal expansion of haematopoietic stem cells among atomic‐bomb survivors. Therefore, radiation exposure might accelerate aging‐associated clonal haematopoiesis, which could result in a long‐lasting elevation of circulating monocytes.

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“…Iatrogenic causes (eg, cytokine therapy, steroids, ziprasidone, and radiation therapy) 21,[32][33][34][35] Cutaneous myeloid dendritic cell dyscrasia 36 Myeloid malignancies (eg, MPN, MDS, MDS/MPN, and AML) 21,37 Lymphoid and plasma cell malignancies (eg, B cell and T cell types) 21,[38][39][40] Solid tumors (eg, carcinoma) 41 rare cases with a previous documented history of MPN and new onset monocytosis, a diagnosis of CMML should not be made. 2 Despite the ongoing discovery of somatic mutations in myeloid malignancies and greater availability of molecular genetic testing, the utility of mutations in the diagnosis CMML is still limited.…”

Section: Postsplenectomy 31mentioning

confidence: 99%

How I investigate monocytosis

Lynch

Hall

Foucar

2018

Int J Lab Hematology

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Monocytosis is a common finding that is caused by a wide variety of neoplastic and non-neoplastic conditions. The adequate evaluation of monocytosis involves the integration of laboratory data, morphology, clinical findings, and the judicious use of ancillary studies. We review the literature on monocytosis, including the 2017 revised 4th edition of the World Health Organization classification of hematopoietic neoplasms.We present a review of monocytosis with practical guidelines on how to approach both routine and challenging cases. K E Y W O R D Sblood, bone marrow, leukemia, monocytes, morphology, myeloid | INTRODUCTIONCirculating peripheral blood monocytes are key players in the innate immune system. Although not distinct morphologically, dendritic cells and precursors also circulate. These monocytic/dendritic cells are derived primarily from bone marrow hematopoietic stem cells and are highly versatile with capacity to migrate to sites of inflammation, differentiate into tissue macrophages and specialized dendritic cell subtypes, secrete cytokines and chemokines to attract other inflammatory cells, and phagocytose tissue debris and microorganisms. They also participate in the initiation of adaptive immunity by presenting antigens to antigen-specific lymphocytes. The effector functions and roles played by these cells in mediating acute and chronic inflammation, antimicrobial defense, and tissue repair and wound healing are vital to the maintenance of a healthy steady state. When dysfunctional or dysregulated, however, monocytes can contribute to and cause significant disease. The purpose of this review was present a strategy to investigate monocytosis primarily in the adult patient. | BACKGROUNDIn the healthy adult and child, monocytes typically comprise between 1 and 9 percent of total peripheral blood leukocytes, with the absolute

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Monocytosis: A new observation during radiotherapy

Cited by 17 publications

References 12 publications

Non-myeloablative busulfan chimeric mouse models are less pro-inflammatory than head-shielded irradiation for studying immune cell interactions in brain tumours

Non-myeloablative busulfan chimeric mouse models are less pro-inflammatory than head-shielded irradiation for studying immune cell interactions in brain tumours

Radiation exposure and longitudinal changes in peripheral monocytes over 50 years: the Adult Health Study of atomic‐bomb survivors

How I investigate monocytosis

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