Identification of CD68+ neutrophil granulocytes in in vitro model of acute inflammation and inflammatory bowel disease

Amanzada, Ahmad; Malik, Ihtzaz Ahmed; Ramadori, G; Moriconi, Federico

doi:10.1055/s-0033-1352657

Cited by 33 publications

(37 citation statements)

References 25 publications

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“…We also found that CD68 ϩ neutrophils comprised a significant proportion (17.7%) of the DPA-713 ϩ cells. Gottfried et al and Amanzada et al demonstrated that CD68 is not specific to macrophages and is a lysosomal protein enriched in activated macrophages, dendritic cell, granulocytes, and some fibroblasts (33,34). We also found that 18% of DPA-713 ϩ cells were CD11b ϩ Gr-1 ϩ inflammatory macrophages.…”

Section: Discussionsupporting

confidence: 69%

Radioiodinated DPA-713 Imaging Correlates with Bactericidal Activity of Tuberculosis Treatments in Mice

Ordoñez

Pokkali

DeMarco

et al. 2015

Antimicrob Agents Chemother

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Current tools for monitoring response to tuberculosis treatments have several limitations. Noninvasive biomarkers could accelerate tuberculosis drug development and clinical studies, but to date little progress has been made in developing new imaging technologies for this application. In this study, we developed pulmonary single-photon emission computed tomography (SPECT) using radioiodinated DPA-713 to serially monitor the activity of tuberculosis treatments in live mice, which develop necrotic granulomas and cavitary lesions. C3HeB/FeJ mice were aerosol infected with Mycobacterium tuberculosis and administered either a standard or a highly active bedaquiline-containing drug regimen. Recognizing that tuberculosis (TB) is still a leading cause of human death from a curable disease, the international health community has set an ambitious target to eliminate TB by 2050. However, using mathematical modeling, Dye and Williams at the World Health Organization have shown that while most TB patients can be cured with current drug treatments, the 2050 target cannot be achieved with current tools and requires a combination of new diagnostics, shorter TB drug treatments, and new vaccines (1). However, current tools for evaluating TB therapeutics have several limitations. Conventional preclinical studies are limited to analysis of serial postmortem samples using microbiologic methods that take 3 to 4 weeks for results. Moreover, different groups of animals are sacrificed over several time points during the study, and therefore, assessments of disease in the same animal can never be made. Similar limitations exist for monitoring TB treatments in humans. The standard 8-week sputum culture conversion is not available in real time, taking several weeks for results. Even though nucleic acid amplification tests such as GeneXpert provide results rapidly (2), both sputum culture and GeneXpert are subject to sampling bias and provide information only about the lesions communicating with the airways. Noncommunicating pulmonary or extrapulmonary lesions are often never assessed. Similarly, assessment for relapse can require monitoring hundreds of patients for up to 2 years after treatment completion. With increasing rates of multidrug-resistant, extensively drug-resistant, and totally drug-resistant TB (3, 4), it is imperative to develop even better tools to monitor treatment responses and predict relapse.Noninvasive imaging provides rapid, three-dimensional views of the whole body, as well as the ability to monitor disease in the same individual. Real-time, longitudinal assessments can also provide new insights into the pathophysiology of disease, which may be difficult to assess with current technologies. Computed tomography (CT) and 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET) are being increasingly used to monitor TB (5-8), in both preclinical and clinical settings. However, both CT and 18 F-FDG PET lack specificity, and 18 F-FDG is taken up by all glycolytically active tissues (9-11). Since activated m...

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Section: Discussionsupporting

confidence: 69%

Radioiodinated DPA-713 Imaging Correlates with Bactericidal Activity of Tuberculosis Treatments in Mice

Ordoñez

Pokkali

DeMarco

et al. 2015

Antimicrob Agents Chemother

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“…Although CD68 is considered a marker of macrophages, recent evidence indicates that CD68 could be expressed in some conditions by other cells, such as dendritic cells, neutrophils and fibroblasts (Amanzada et al, 2013;Gottfried et al, 2008). We found that CD68+ cells identified in the papillary dermis of the skin analyzed co-expressed the macrophage marker CD163 ( Figure 3C Figure 4A).…”

Section: Il-17e Positive Cells Are Over-represented In the Dermis Of mentioning

confidence: 55%

Keratinocyte-Derived IL-17E Contributes to Inflammation in Psoriasis

Senra

Stalder

Martínez

et al. 2016

Journal of Investigative Dermatology

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Psoriasis is a chronic inflammatory skin disorder effectively treated by blocking IL-17RA, a receptor chain used by several IL-17 family members, including IL-17E. Although IL-17A is critically involved in the pathogenesis of psoriasis, the contribution of IL-17E remains unknown. Here we show that IL-17E(+) cells are more abundant than IL-17A(+) cells in lesional psoriatic skin. IL-17E synthesis is increased in keratinocytes within psoriatic plaques, and macrophages having a mixed M1/M2 phenotype represent an important proportion of the IL-17E(+) cells infiltrating the dermis. Mechanistically, macrophages do not synthetize but rather take up IL-17E via receptor-mediated clathrin-dependent endocytosis. Furthermore, monocyte-derived macrophages in vitro polarized in M2, but not M1, express the IL-17E receptor and respond to IL-17E by preferentially producing inflammatory cytokines and chemokines involved in neutrophil recruitment. Remarkably, IL-17E expression in lesional psoriatic skin correlates with the number of neutrophils while being inversely proportional to the number of infiltrating T cells. These data provide strong evidence for a proinflammatory role of keratinocyte-derived IL-17E in psoriasis, possibly via macrophage activation.

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“…A recent study from Amanzada et al demonstrated CD68 mRNA expression in neutrophils isolated from patients with inflammatory bowel disease. 54 The observation that a greater percentage of bone marrow neutrophils expressed GFP than within the mobilized blood neutrophil population may indicate carryover of GFP expression from a shared progenitor population. Flow cytometric phenotyping using antibodies directed against the CXCR2 and CXCR4 chemokine receptors showed that GFP expression by neutrophils in the blood of CD68-GFP mice may be able to inform of neutrophil subsets, with the newly mobilized CXCR4 LO neutrophils showing high GFP expression compared with GFP 2 CXCR4 expressing senescent neutrophil population 55 (supplemental Figure 4).…”

Section: Discussionmentioning

confidence: 99%

Human CD68 promoter GFP transgenic mice allow analysis of monocyte to macrophage differentiation in vivo

Iqbal

McNeill

Kapellos

et al. 2014

Blood

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• CD68-GFP reporter mice show GFP transgene expression in both monocytes and tissue resident macrophage populations.• Adoptively transferred CD68-GFP monocytes maintain GFP expression after recruitment in an ongoing inflammatory response.The recruitment of monocytes and their differentiation into macrophages at sites of inflammation are key events in determining the outcome of the inflammatory response and initiating the return to tissue homeostasis. To study monocyte trafficking and macrophage differentiation in vivo, we have generated a novel transgenic reporter mouse expressing a green fluorescent protein (GFP) under the control of the human CD68 promoter. CD68-GFP mice express high levels of GFP in both monocyte and embryoderived tissue resident macrophages in adult animals. The human CD68 promoter drives GFP expression in all CD115 1 monocytes of adult blood, spleen, and bone marrow; we took advantage of this to directly compare the trafficking of bone marrow-derived CD68-GFP monocytes to that of CX 3 CR1 GFP monocytes in vivo using a sterile zymosan peritonitis model. Unlike CX 3 CR1 GFP monocytes, which downregulate GFP expression on differentiation into macrophages in this model, CD68-GFP monocytes retain high-level GFP expression for 72 hours after differentiation into macrophages, allowing continued cell tracking during resolution of inflammation. In summary, this novel CD68-GFP transgenic reporter mouse line represents a powerful resource for analyzing monocyte mobilization and monocyte trafficking as well as studying the fate of recruited monocytes in models of acute and chronic inflammation. (Blood. 2014;124(15):e33-e44)

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Identification of CD68+ neutrophil granulocytes in in vitro model of acute inflammation and inflammatory bowel disease

Cited by 33 publications

References 25 publications

Radioiodinated DPA-713 Imaging Correlates with Bactericidal Activity of Tuberculosis Treatments in Mice

Radioiodinated DPA-713 Imaging Correlates with Bactericidal Activity of Tuberculosis Treatments in Mice

Keratinocyte-Derived IL-17E Contributes to Inflammation in Psoriasis

Human CD68 promoter GFP transgenic mice allow analysis of monocyte to macrophage differentiation in vivo

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