The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Poels, Lambert G. - One of the best experts on this subject based on the ideXlab platform.
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Erythroblasts (bone marrow, rabbit)
2007Co-Authors: Poels, Lambert G.Abstract:Electron microscopy. (1) shows basophilic erythroblasts or early normoblasts with clumped heterochromatin in the nucleus and numerous polysomes. (1m) points to a mitotic figure of a basophilic erythroblast. A late polychromatic erythroblast or intermediate normoblast (2) marks a maturing stage in which the hemoglobin synthesis starts and the cytoplasm is more electron-dense. There is a decrease in amount of all organelles and nuclear clumping starts to take place. (3) young Myelocytes. (C) capillary; (R) part of a reticular cell
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Neutrophilic myelopoiesis in bone marrow smear (human)
2007Co-Authors: Poels, Lambert G.Abstract:Stain: May-Grnwald-Giemsa (MGG). A group of neutrophilic myeloid cells are clustered together. (1) late myeloblast with nucleoli and hardly any azurophilic granules. (2) proMyelocytes as the largest cells of the series, with ample cytoplasm filled with many azurophilic granules. (3) Myelocytes with the nucleus shifted to one side of the cell. (4) metaMyelocytes with indentations of the nucleus as a first step towards band forms. (5) segmentation of the nucleus progresses in (6)
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Three basophilic erythroblasts in bone marrow smear (human)
2007Co-Authors: Poels, Lambert G.Abstract:Stain: May-Grnwald-Giemsa (MGG). Three basophilic erythroblasts (1) with intense blue stained cytoplasm, and some so called ears or cytoplasmic projections (arrows). Chromatin strands are thicker than in the proerythroblast. Generally no nucleoli are seen. (2) Damaged or smudged eosinophilic Myelocyte
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Plasma cell in bone marrow smear (human)
2007Co-Authors: Poels, Lambert G.Abstract:Stain: May-Grnwald-Giemsa (MGG). (1) A plasma cell with vacuoles (containing Ig), basophilic cytoplasm and a clear halo (Golgi apparatus) in a bone marrow film. (2) represents a young polychromatic erythroblast. (3) neutrophilic Myelocyte, and (4) is a cluster of platelets
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Shift to the left response of granulocytes in blood smear (human)
2007Co-Authors: Poels, Lambert G.Abstract:Stain: May-Grnwald-Giemsa (MGG). During infection a shift towards a relative increase of the number of neutrophilic granulocytes (3) with reduced lobulation of the nuclei and immature white cells, occurs in blood. (1) promonocyte. (2) (pro)Myelocyte
John I. Gallin - One of the best experts on this subject based on the ideXlab platform.
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Brief Definitive Report Neutrophil-specific Granule Deficiency Results from a Novel Mutation with Loss of Function of the Transcription Factor CCAAT/Enhancer Binding Protein �
2013Co-Authors: A. Lekstrom-himes, Susan E. Dorman, Piroska Kopar, Steven M. Holl, John I. GallinAbstract:Neutrophil-specific granule deficiency (SGD) is a rare disorder characterized by recurrent pyogenic infections, defective neutrophil chemotaxis and bactericidal activity, and lack of neutrophil secondary granule proteins. CCAAT/enhancer binding protein (C/EBP)�, a member of the leucine zipper family of transcription factors, is expressed primarily in myeloid cells, and its knockout mouse model possesses distinctive defects, including a lack of neutrophil secondary granule proteins. Sequence analysis of the genomic DNA of a patient with SGD revealed a five-basepair deletion in the second exon of the C/EBP � locus. The predicted frame shift results in a truncation of the 32-kD major C/EBP � isoform, with loss of the dimerization domain, DNA binding region, and transcriptional activity. The multiple functional defects observed in these early neutrophil progenitor cells, a consequence of C/EBP � deficiency, define SGD as a defect in myelopoiesis and establish the requirement for C/EBP � for the proMyelocyte–Myelocyte transition in myeloid differentiation. Key words: myelopoiesis • lactoferrin • granulocyte • immunodeficiency • neutrophil Neutrophil-specific granule deficiency (SGD) is a rare congenital disorder marked by frequent and sever
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neutrophil specific granule deficiency results from a novel mutation with loss of function of the transcription factor ccaat enhancer binding protein e
Journal of Experimental Medicine, 1999Co-Authors: Julie A Lekstromhimes, Susan E. Dorman, Steven M Holland, Piroska Kopar, John I. GallinAbstract:Neutrophil-specific granule deficiency (SGD) is a rare disorder characterized by recurrent pyogenic infections, defective neutrophil chemotaxis and bactericidal activity, and lack of neutrophil secondary granule proteins. CCAAT/enhancer binding protein (C/EBP)e, a member of the leucine zipper family of transcription factors, is expressed primarily in myeloid cells, and its knockout mouse model possesses distinctive defects, including a lack of neutrophil secondary granule proteins. Sequence analysis of the genomic DNA of a patient with SGD revealed a five-basepair deletion in the second exon of the C/EBPe locus. The predicted frame shift results in a truncation of the 32-kD major C/EBPe isoform, with loss of the dimerization domain, DNA binding region, and transcriptional activity. The multiple functional defects observed in these early neutrophil progenitor cells, a consequence of C/EBPe deficiency, define SGD as a defect in myelopoiesis and establish the requirement for C/EBPe for the proMyelocyte–Myelocyte transition in myeloid differentiation.
Jan Ake Lindgren - One of the best experts on this subject based on the ideXlab platform.
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inverse relationship between myeloid maturation and leukotriene c4 synthase expression in normal and leukemic myelopoiesis consistent overexpression of the enzyme in myeloid cells from patients with chronic myeloid leukemia
Experimental Hematology, 2003Co-Authors: Susanne Tornhamre, Leif Stenke, Anna Granzelius, Mikael Sjolinder, Barbro Nasmanglaser, Cecilia Roos, Susanne Widell, Jan Ake LindgrenAbstract:Abstract Objective Leukotriene (LT) C 4 synthase (LTC 4 S) is the key enzyme in the biosynthesis of LTC 4 , which has been reported to stimulate the growth of human myeloid progenitor cells and is specifically overproduced in chronic myeloid leukemia (CML). The aim of this study was to clarify the expression of LTC 4 S during normal and leukemic myelopoiesis and to investigate the correlation between abnormal LTC 4 S expression in CML myeloid cells and the activity of the disease-specific tyrosine kinase p210 BCR-ABL. Materials and Methods Immature and mature myeloid cell subpopulations were isolated with magnetic cell sorting from healthy volunteer bone marrow (n = 11) and CML patient peripheral blood (n = 8), respectively. The cells were subjected to analysis of LTC 4 S protein expression and activity. Expression of LTC 4 S was investigated in CD16 + neutrophils from CML patients before and after 1 month of medication with imatinib mesylate (STI571), which is a specific inhibitor of p210 BCR-ABL. Results Among normal cells, the highest enzyme activity was observed in the most immature, CD34 + progenitor cell-enriched and CD15 + Myelocyte-enriched fractions. Subsequently, LTC 4 S activity decreased with increasing maturity, with only negligible amounts of LTC 4 produced in CD16 + neutrophils. LTC 4 S was expressed at the protein level in the immature myeloid cell fractions but not in CD16 + cells. In CML cells, LTC 4 S activity and expression were consistently elevated. Thus, the CML CD34 + and CD15 + cell fractions, as well as the CD11b + Myelocyte/metaMyelocyte-enriched fractions, produced 6 to 10 times as much LTC 4 as the corresponding normal cells. Again, enzyme expression was highest in the most immature cells, although evident LTC 4 S expression and activity remained in CML CD16 + neutrophils. Interestingly, treatment of five CML patients with imatinib mesylate down-regulated the abnormal neutrophil LTC 4 S expression and activity. Conclusions Expression of LTC 4 S in immature myelopoid cells is in line with a role for this enzyme in myelopoiesis. In addition, consistent overexpression of LTC 4 S in CML and the correlation to p210 BCR-ABL activity suggests that LTC 4 S may be involved in leukemic pathogenesis.
Niels Borregaard - One of the best experts on this subject based on the ideXlab platform.
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Expression of miR-941, KDM6B mRNA, and PRTN3 mRNA during human granulopoiesis.
2016Co-Authors: Jesper Brink Svendsen, Niels Borregaard, Bo Baslund, Elisabeth Præstekjær Cramer, Nicolas Rapin, Jack Bernard CowlandAbstract:Relative expression of miR-941 (circles), KDM6B mRNA (crosses), and PRTN3 mRNA (triangles) in myeloblasts and proMyelocytes (MB&PM), Myelocytes and metaMyelocytes (MC&MM), band cells and segmented cells (BC&SC), and PMNs, respectively. Data are from our previous global expression analyses of mRNAs [12,17] and miRNAs [8] during granulopoiesis. For all three RNAs, data are shown relative to the cell population with the highest expression, which is given the value 1. Error bars are mean ± SD.
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ficolin 1 is present in a highly mobilizable subset of human neutrophil granules and associates with the cell surface after stimulation with fmlp
Journal of Leukocyte Biology, 2009Co-Authors: Sara Rørvig, Christian Honoré, Larsinge Larsson, Sophie Ohlsson, Corinna Cavan Pedersen, Lars C Jacobsen, Niels BorregaardAbstract:Ficolins are soluble molecules that bind carbohydrate present on the surface of microorganisms and function as recognition molecules in the lectin complement pathway. Three ficolins have been identified in humans: ficolin-1, ficolin-2, and ficolin-3. Ficolin-1 is synthesized in monocytes and type II alveolar epithelial cells. Ficolin-1 has been shown to be present in secretory granules of human neutrophils, but it is not known which subset of the neutrophils' secretory granules harbors ficolin-1. To determine the exact subcellular localization of ficolin-1 in neutrophils, recombinant ficolin-1 was expressed in Chinese hamster ovary cells and used for generation of polyclonal antibodies. This allowed detection of ficolin-1 in subcellular fractions of human neutrophils by ELISA, by Western blotting, and by immunohistochemistry. Real-time PCR examination of normal human bone marrow showed FCN1 gene expression largely in Myelocytes, metaMyelocytes, and band cells with a profile quite similar to that of gelatinase. In accordance with this, biosynthesis studies of neutrophils precursor cells showed that ficolin-1 was primarily synthesized in Myelocytes, metaMyelocytes, and band cells. Immunohistochemistry and subcellular fractionation demonstrated that ficolin-1 is primarily localized in gelatinase granules but also in highly exocytosable gelatinase-poor granules, not described previously. Ficolin-1 is released from neutrophil granules by stimulation with fMLP or PMA, and the majority becomes associated with the surface membrane of the cells and can be detected by flow cytometry. Our studies show that neutrophils are a major source of ficolin-1, which can be readily exocytosed by stimulation.
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the secretory leukocyte protease inhibitor slpi and the secondary granule protein lactoferrin are synthesized in Myelocytes colocalize in subcellular fractions of neutrophils and are coreleased by activated neutrophils
Journal of Leukocyte Biology, 2008Co-Authors: Lars C Jacobsen, Niels Borregaard, Ole E Sorensen, Kim TheilgaardmonchAbstract:The secretory leukocyte protease inhibitor (SLPI) re-establishes homeostasis at sites of infection by virtue of its ability to exert antimicrobial activity, to suppress LPS-induced cellular immune responses, and to reduce tissue damage through inhibition of serine proteases released by polymorphonuclear neutrophil granulocytes (PMNs). Microarray analysis of bone marrow (BM) populations highly enriched in proMyelocytes, Myelocytes/metaMyelocytes (MYs), and BM neutrophils demonstrates a transient, high mRNA expression of SLPI and genuine secondary granule proteins (GPs) in MYs. Consistent with this finding, immunostaining of BM cells showed SLPI and the secondary GP lactoferrin (LF) to be present in cells from the Myelocyte stage and throughout neutrophil differentiation. Subcellular fractionation studies demonstrated the colocalization of SLPI and LF in subcellular fractions highly enriched in secondary granules. Finally, exocytosis studies demonstrated a corelease of SLPI and LF within minutes of activation. Collectively, these findings strongly indicate that SLPI is localized in secondary granules of PMNs. However, the amount of SLPI detected in PMNs is low compared with primary keratinocytes stimulated by growth factors involved in wound healing. This implicates that neutrophil-derived SLPI might not contribute essentially to re-establishment of homeostasis at sites of infection but rather, exert physiologically relevant intracellular activities. These might include the protection of secondary GPs against proteolytic activation and/or degradation by proteases, which might be dislocated to secondary granules at minute amounts as a consequence of spillover.
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arginase 1 is expressed in Myelocytes metaMyelocytes and localized in gelatinase granules of human neutrophils
Blood, 2007Co-Authors: Lars C Jacobsen, Erik Ilsø Christensen, Kim Theilgaardmonch, Niels BorregaardAbstract:Arginase 1 (ARG1) metabolizes arginine, thus reducing the availability of arginine as a substrate for nitric oxide synthase (NOS). The decreased production of nitric oxide (NO) by NOS and the production of ornithine by ARG1 affect immune responses and tissue regeneration at sites of infection, respectively. We here demonstrate that ARG1 is synthesized in Myelocytes/metaMyelocytes and is stored in gelatinase granules. In accordance with this, activated neutrophils coreleased ARG1 and gelatinase to the extracellular environment on stimulation with phorbol-12-myristate 13-acetate (PMA), formyl-methionyl-leucyl-phenylalanine (fMLP), or tumor necrosis factor α (TNF-α). Overall, these findings define ARG1 as a genuine gelatinase granule protein and support a model in which activated neutrophils release ARG1 at sites of infection to modulate immune responses and promote tissue regeneration.
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defensin rich granules of human neutrophils characterization of secretory properties
Biochimica et Biophysica Acta, 2002Co-Authors: Mikkel Faurschou, Ole E Sorensen, Anders H Johnsen, Jon Askaa, Niels BorregaardAbstract:The various granule subtypes of the human neutrophil differ in propensity for exocytosis. As a rule, granules formed at late stages of myelopoiesis have a higher secretory potential than granules formed in more immature myeloid cells. Neutrophils contain four closely related alpha-defensins, which are stored in a subset of azurophil granules. These defensin-rich azurophil granules (DRG) are formed later than defensin-poor azurophil granules, near the proMyelocyte/Myelocyte transition. In order to characterize the secretory properties of DRG, we developed a sensitive and accurate ELISA for detection of the neutrophil alpha-defensins HNP 1-3. This allowed us to quantify the exocytosis of alpha-defensins and markers of azurophil (myeloperoxidase), specific (lactoferrin) and gelatinase (gelatinase) granules from neutrophils stimulated with different secretagogues. The release pattern of alpha-defensins correlated perfectly with the release of myeloperoxidase and showed no resemblance to the exocytosis of lactoferrin or gelatinase. This finding was substantiated through subcellular fractionation experiments. In conclusion, despite a distinct profile of biosynthesis, DRG are indistinguishable from defensin-poor azurophil granules with respect to exocytosis. Thus, in contrast to peroxidase-negative granules, azurophil granules display homogeneity in their availability for extracellular release.
Julie A Lekstromhimes - One of the best experts on this subject based on the ideXlab platform.
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neutrophil specific granule deficiency results from a novel mutation with loss of function of the transcription factor ccaat enhancer binding protein e
Journal of Experimental Medicine, 1999Co-Authors: Julie A Lekstromhimes, Susan E. Dorman, Steven M Holland, Piroska Kopar, John I. GallinAbstract:Neutrophil-specific granule deficiency (SGD) is a rare disorder characterized by recurrent pyogenic infections, defective neutrophil chemotaxis and bactericidal activity, and lack of neutrophil secondary granule proteins. CCAAT/enhancer binding protein (C/EBP)e, a member of the leucine zipper family of transcription factors, is expressed primarily in myeloid cells, and its knockout mouse model possesses distinctive defects, including a lack of neutrophil secondary granule proteins. Sequence analysis of the genomic DNA of a patient with SGD revealed a five-basepair deletion in the second exon of the C/EBPe locus. The predicted frame shift results in a truncation of the 32-kD major C/EBPe isoform, with loss of the dimerization domain, DNA binding region, and transcriptional activity. The multiple functional defects observed in these early neutrophil progenitor cells, a consequence of C/EBPe deficiency, define SGD as a defect in myelopoiesis and establish the requirement for C/EBPe for the proMyelocyte–Myelocyte transition in myeloid differentiation.
