scholarly journals Terminally Differentiating Eosinophils Express Neutrophil Primary Granule Proteins as well as Eosinophil-specific Granule Proteins in a Temporal Manner

2017 ◽  
Vol 17 (6) ◽  
pp. 410 ◽  
Author(s):  
Karam Kim ◽  
Sae Mi Hwang ◽  
Sung Min Kim ◽  
Sung Woo Park ◽  
Yunjae Jung ◽  
...  
Keyword(s):  
Specific Granule ◽  
Granule Proteins ◽  
Primary Granule

IL-3 Inhibits Terminal Granulocytic Differentiation by Inducing the Binding of Stabilizing Proteins to a 300 Base Pair Region within p21cip1/waf1 Messenger RNA.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3152-3152
Author(s):  
Louis Ghanem ◽  
Richard A. Steinman
Keyword(s):  
Progenitor Cells ◽  
Adaptor Protein ◽  
Proteinase 3 ◽  
Granulocytic Differentiation ◽  
Induced Differentiation ◽  
Aberrant Expression ◽  
P21 Protein ◽  
Mrna Stabilization ◽  
Granule Proteins ◽  
Primary Granule

Abstract Elevated levels of the molecular adaptor protein p21cip1/waf1 (p21) and of the IL-3 receptor α chain are correlated with chemoresistance and poor prognosis in acute myeloid leukemia (AML). p21 is a core regulator of many biological functions including cell cycle control, apoptosis and differentiation. Our laboratory has demo−nstrated that p21 undergoes dynamic changes in expression levels and subcellular compartmentalization during cytokine-induced granulocytic differentiation, suggesting that p21 may play an important role in myeloid development. Based on our observation that p21 protein levels decrease during granulocytic differentiation of CD34+ human progenitor cells, we hypothesized that p21 antagonizes granulopoiesis. The proliferative cytokine IL-3 is required to maintain the undifferentiated state in murine 32Dcl3 cells and has been shown to slow the kinetics of differentiation of normal human myeloid progenitors (Hevehan DL, 2000). Given that 32Dcl3 myeloblasts express high basal levels of p21, we also hypothesized that IL-3 inhibition of 32Dcl3 differentiation is mediated in part by p21. Our findings demonstrate that siRNA knockdown of murine p21 is correlated with premature expression of the primary granule proteins myeloperoxidase and proteinase-3 that are normally not abundant in cells maintained as myeloblasts by IL-3. Rescue of p21 knockdown myeloblasts with human p21 suppressed aberrant expression of granule proteins. The upregulation of myeloperoxidase and proteinase-3 occurred at a posttranscriptional level. These findings indicated that p21 prevented premature expression of primary granule proteins and may contribute to maintenance of the myeloblast phenotype. p21 knockdown was also found to accelerate morphologic granulocytic differentiation in 32Dcl3 cells stimulated with G-CSF, indicating that p21 antagonized the entire differentiation process rather than only suppressing primary granule proteins. We then determined how IL-3 maintains p21 expression in myeloblast cells. We demonstrated that IL-3 stabilized p21 mRNA in myeloblasts leading to high levels of p21 protein. This effect mapped to the 3′ untranslated region (UTR) of the p21 transcript. IL-3 also rescued the decrease in p21 mRNA stability noted during G-CSF-induced differentiation. This has been shown to coincide with differentiation blockade. p21 transcript stabilization by IL-3 was independent of PI3-kinase and ERK pathway signaling. In vitro binding assays provided evidence that distinct sets of RNA:protein interactions occur within the proximal 303 nucleotides of the p21 3′ UTR and are regulated by IL-3 and G-CSF signaling. Association of a ~60–65 kDa protein with p21 riboprobes correlated with IL-3 mediated p21 mRNA stabilization, whereas binding by a ~40–42 kDa protein was associated with destabilization of p21 transcripts in 32Dcl3 cells undergoing G-CSF-induced differentiation. These findings provide the first evidence for IL-3-mediated stabilization of mRNA transcripts in myeloid progenitor cells. The finding that p21 antagonized granulopoiesis is also novel. Because high levels of the IL-3 receptor and high p21 expression have separately been linked to poor outcomes in AML, IL-3 mediated p21 mRNA stabilization may contribute to differentiation blockade during AML pathogenesis.

scholarly journals Neutrophil-specific Granule Deficiency Results from a Novel Mutation with Loss of Function of the Transcription Factor CCAAT/Enhancer Binding Protein ε

1999 ◽  
Vol 189 (11) ◽  
pp. 1847-1852 ◽  
Author(s):  
Julie A. Lekstrom-Himes ◽  
Susan E. Dorman ◽  
Piroska Kopar ◽  
Steven M. Holland ◽  
John I. Gallin
Keyword(s):  
Novel Mutation ◽  
Binding Protein ◽  
Loss Of Function ◽  
Dimerization Domain ◽  
Knockout Mouse Model ◽  
Enhancer Binding Protein ◽  
Ccaat Enhancer Binding Protein ◽  
Specific Granule ◽  
Granule Proteins ◽  
Secondary Granule

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)ε, 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/EBPε locus. The predicted frame shift results in a truncation of the 32-kD major C/EBPε 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/EBPε deficiency, define SGD as a defect in myelopoiesis and establish the requirement for C/EBPε for the promyelocyte–myelocyte transition in myeloid differentiation.

Expression of Azurophil and specific granule proteins during differentiation of NB4 cells in neutrophils

1998 ◽  
Vol 175 (2) ◽  
pp. 203-210 ◽  
Author(s):  
Christine Grégoire ◽  
Heidi Welch ◽  
Catherine Astarie-Dequeker ◽  
Isabelle Maridonneau-Parini
Keyword(s):  
Nb4 Cells ◽  
Specific Granule ◽  
Granule Proteins

scholarly journals In vitro Induction of Myeloid Leukemia–Specific CD4 and CD8 T Cells by CD40 Ligand – Activated B Cells Gene Modified to Express Primary Granule Proteins

2005 ◽  
Vol 11 (12) ◽  
pp. 4495-4503 ◽  
Author(s):  
Hiroshi Fujiwara ◽  
J. Joseph Melenhorst ◽  
Frank El Ouriaghli ◽  
Sachiko Kajigaya ◽  
Matthias Grube ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Cd8 T Cells ◽  
Myeloid Leukemia ◽  
Cd40 Ligand ◽  
Granule Proteins ◽  
In Vitro Induction ◽  
Primary Granule ◽  
Activated B Cells

Deficiency of the specific granule proteins, R-binder/transcobalamin I and lactoferrin, in plasma and saliva: A new disorder

2001 ◽  
Vol 100 (2) ◽  
pp. 145-151 ◽  
Author(s):  
Judith C. Lin ◽  
Niels Borregaard ◽  
Howard A. Liebman ◽  
Ralph Carmel
Keyword(s):  
Specific Granule ◽  
Granule Proteins ◽  
Transcobalamin I

scholarly journals Sorting of the Specific Granule Protein, NGAL, During Granulocytic Maturation of HL-60 Cells

Blood ◽  
1997 ◽  
Vol 89 (6) ◽  
pp. 2113-2121 ◽  
Author(s):  
Véronique Le Cabec ◽  
Jero Calafat ◽  
Niels Borregaard
Keyword(s):  
Human Neutrophil ◽  
Cell Stage ◽  
Cytomegalovirus Promoter ◽  
Granule Protein ◽  
Transport Vesicles ◽  
Different Types ◽  
Storage Granules ◽  
Specific Granule ◽  
Granule Proteins

Abstract The different types of human neutrophil granules (azurophil, specific, and gelatinase granules) are formed sequentially during maturation of neutrophils from the promyelocyte stage to the band cell stage. The promyelocytic HL-60 cells can maturate to segmented granulocytes but are incapable of activating the transcription of any known intragranular protein, normally located in specific or gelatinase granules. To study the sorting of granule proteins during maturation, we transfected HL-60 cells with the specific granule protein NGAL, inserted under control of a cytomegalovirus promoter. We previously showed that NGAL is sorted to azurophil granules and colocalizes with myeloperoxidase in undifferentiated HL-60 cells. We show here that, when such transfected HL-60 cells differentiate into granulocytes, newly synthesized NGAL is not retained in granules but is constitutively secreted. This indicates that highly specific mechanisms must exist that are responsible for diverting transport vesicles into storage granules, and that HL-60 cells not only lack the ability to activate transcription of specific granule proteins, but also lose the ability to form storage granules during maturation.

scholarly journals Neutrophil-specific granule deficiency includes eosinophils

Blood ◽  
1993 ◽  
Vol 82 (1) ◽  
pp. 268-273 ◽  
Author(s):  
HF Rosenberg ◽  
JI Gallin
Keyword(s):  
White Blood Cells ◽  
Eosinophil Cationic Protein ◽  
Cell Lineage ◽  
Cationic Protein ◽  
Peripheral Cell ◽  
Gm Csf ◽  
Specific Granule ◽  
Granule Proteins ◽  
Macrophage Colony ◽  
Peripheral White Blood Cells

Neutrophil-specific granule deficiency is a disorder of leukocyte maturation associated with decreased levels of mRNA for a distinct subset of granule proteins. Our work indicates that this disorder, previously thought to be limited to the neutrophil lineage, can also include eosinophils. Immunofluorescence staining led to the discovery of a small but distinct population of peripheral white blood cells containing eosinophil peroxidase (EPO). Unlike normal eosinophils, these EPO+ cells do not have large, eosin-staining cytoplasmic granules, and are indistinguishable from granule-deficient neutrophils by light microscopy. The EPO+ cell lineage did resemble the normal eosinophil lineage in its ability to respond dramatically to granulocyte-macrophage colony-stimulating factor (GM-CSF); the size of the EPO+ peripheral cell population increased approximately 70-fold over baseline in response to GM-CSF administration. The EPO+ cells contained eosinophil Charcot-Leyden crystal protein, but were deficient in three eosinophil-specific granule proteins; neither eosinophil cationic protein, eosinophil-derived neurotoxin, nor major basic protein could be detected in these EPO+ cells, despite the presence of mRNA transcripts for each of the three absent proteins.

scholarly journals Neutrophil primary granule proteins HBP and HNP1–3 boost bacterial phagocytosis by human and murine macrophages

2008 ◽  
Vol 118 (10) ◽  
pp. 3491-3502 ◽  
Author(s):  
Oliver Soehnlein ◽  
Ylva Kai-Larsen ◽  
Robert Frithiof ◽  
Ole E. Sorensen ◽  
Ellinor Kenne ◽  
...  
Keyword(s):  
Murine Macrophages ◽  
Granule Proteins ◽  
Primary Granule

scholarly journals Mechanism of dexamethasone inhibition of chemotactic factor induced granulocyte aggregation

Blood ◽  
1982 ◽  
Vol 59 (2) ◽  
pp. 265-269
Author(s):  
RS Oseas ◽  
J Allen ◽  
HH Yang ◽  
RL Baehner ◽  
LA Boxer
Keyword(s):  
Cytochalasin B ◽  
Chemotactic Factor ◽  
Human Lactoferrin ◽  
Endothelial Monolayers ◽  
Aggregation Response ◽  
Specific Granule ◽  
Primary Granule

The reaction of FMLP with granulocytes causes aggregation and degranulation and enhances adherence to endothelium. To evaluate whether prevention of granule extrusion could impair these granulocyte activities, granulocytes were treated with either dexamethasone or hydrocortisone prior to treatment with FMLP. Dexamethasone was added to suspensions of cytochalasin B-treated granulocytes; it markedly impaired the aggregation response of the granulocytes of FMLP. When cytochalasin-B was not used, granulocyte aggregation in response to FMLP or PMA was inhibited by dexamethasone. Although dexamethasone prevented aggregation of cells following stimulation with FMLP or PMA, it failed to prevent the aggregation of granulocytes induced by rabbit lactoferrin. Adherence of granulocytes to human endothelial monolayers was enhanced by FMLP; dexamethasone inhibited the enhancement. However, with the addition of human lactoferrin to the granulocytes exposed to dexamethasone, the cells were able to adhere as well to endothelium as the cells exposed to FMLP but free of dexamethasone. When cytochalasin- B-treated granulocytes were incubated with dexamethasone or hydrocortisone prior to the addition of FMLP, the subsequent release of lactoferrin was substantially blocked, whereas the release of the primary granule products, lysozyme and beta-glucuronidase, was attenuated but not completely blocked. Thus, corticosteroids might block chemotactic-factor-induced granulocyte aggregation by selectively preventing release of specific granule products that contribute to and sustain aggregation.

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