Subcellular localization and mobilization of carcinoembryonic antigen‐related cell adhesion molecule 8 in human neutrophils

Zhao, Liyan; Furebring, Mia; Xu, Shaoyuan

doi:10.1111/j.1365-2141.2004.04963.x

Cited by 18 publications

(15 citation statements)

References 38 publications

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“…1h ). Zhao et al estimated the total cellular content of CEACAM8 in granulocytes to be 82.4+/−8.9 ng/10 6 cells (mean +/− SE, n = 10), [20]. In our study we demonstrated that approximately 0.5–1 ng CEACAM8 was secreted by 1×10 6 granulocytes.…”

Section: Resultssupporting

confidence: 60%

“…These data suggest that the mechanisms regulating the expression of soluble CEACAM6 are different compared to the CpG-ODN-associated regulation of soluble CEACAM8. It is well documented that CEACAM8 is stored in the neutrophilic vesicles and released in response to PMA [10], [20]. To assess the percentage of secreted CEACAM8 in relation to the total amount of cellular CEACAM8, cell lysates of CpG-ODN treated and untreated granulocyte were probed with the CEACAM8 specific mAb 80H3.…”

Section: Resultsmentioning

confidence: 99%

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Soluble CEACAM8 Interacts with CEACAM1 Inhibiting TLR2-Triggered Immune Responses

et al. 2014

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Lower respiratory tract bacterial infections are characterized by neutrophilic inflammation in the airways. The carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 8 is expressed in and released by human granulocytes. Our study demonstrates that human granulocytes release CEACAM8 in response to bacterial DNA in a TLR9-dependent manner. Individuals with a high percentage of bronchial lavage fluid (BALF) granulocytes were more likely to have detectable levels of released CEACAM8 in the BALF than those with a normal granulocyte count. Soluble, recombinant CEACAM8-Fc binds to CEACAM1 expressed on human airway epithelium. Application of CEACAM8-Fc to CEACAM1-positive human pulmonary epithelial cells resulted in reduced TLR2-dependent inflammatory responses. These inhibitory effects were accompanied by tyrosine phosphorylation of the immunoreceptor tyrosine-based inhibitory motif (ITIM) of CEACAM1 and by recruitment of the phosphatase SHP-1, which could negatively regulate Toll-like receptor 2-dependent activation of the phosphatidylinositol 3-OH kinase-Akt kinase pathway. Our results suggest a new mechanism by which granulocytes reduce pro-inflammatory immune responses in human airways via secretion of CEACAM8 in neutrophil-driven bacterial infections.

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Section: Resultssupporting

confidence: 60%

Section: Resultsmentioning

confidence: 99%

Soluble CEACAM8 Interacts with CEACAM1 Inhibiting TLR2-Triggered Immune Responses

et al. 2014

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“…Therefore we specifically searched for other neutrophil-associated genes, to better understand the implication of this granulocyte subtype as an early predictor of GI irAEs. These included genes encoding for granuleassociated proteins such as olfactomedin 4 (OLFM4) [26], azurocidin 1 (AZU1), lactoferrin (LTF) [27], cathelicidin (CAMP), myeloperoxidase (MPO) [28], bactericidal/permeability increasing protein (BPI), defensin (DEFA4) [29], neutrophil elastase (ELANE) [30], cathepsin G (CTSG) [30], CEACAM6, CEACAM8 [31], and CEACAM1 (which mediates neutrophil adhesion to endothelial cells and facilitates their transmigration into tissues) [32]. The GeneChip HT-HG-U133A includes probe sets for many of these genes Additional file 1: Table S3.…”

Section: Association Between Expression Of Cd177 and Other Neutrophilmentioning

confidence: 99%

Gene expression profiling of whole blood in ipilimumab-treated patients for identification of potential biomarkers of immune-related gastrointestinal adverse events

et al. 2013

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BackgroundTreatment with ipilimumab, a fully human anti-CTLA-4 antibody approved for the treatment of advanced melanoma, is associated with some immune-related adverse events (irAEs) such as colitis (gastrointestinal irAE, or GI irAE) and skin rash, which are managed by treatment guidelines. Nevertheless, predictive biomarkers that can help identify patients more likely to develop these irAEs could enhance the management of these toxicities.MethodsTo identify candidate predictive biomarkers associated with GI irAEs, gene expression profiling was performed on whole blood samples from 162 advanced melanoma patients at baseline, 3 and 11 weeks after the start of ipilimumab treatment in two phase II clinical trials (CA184004 and CA184007). Overall, 49 patients developed Grade 2 or higher (grade 2+) GI irAEs during the course of treatment. A repeated measures analysis of variance (ANOVA) was used to evaluate the differences in mean expression levels between the GI irAE and No-GI irAE groups of patients at the three time points.ResultsIn baseline samples, 27 probe sets showed differential mean expression (≥ 1.5 fold, P ≤ 0.05) between the GI irAE and No-GI irAE groups. Most of these probe sets belonged to three functional categories: immune system, cell cycle, and intracellular trafficking. Changes in gene expression over time were also characterized. In the GI irAE group, 58 and 247 probe sets had a ≥ 1.5 fold change in expression from baseline to 3 and 11 weeks after first ipilimumab dose, respectively. In particular, on-treatment expression increases of CD177 and CEACAM1, two neutrophil-activation markers, were closely associated with GI irAEs, suggesting a possible role of neutrophils in ipilimumab-associated GI irAEs. In addition, the expression of several immunoglobulin genes increased over time, with greater increases in patients with grade 2+ GI irAEs.ConclusionsGene expression profiling of peripheral blood, sampled before or early in the course of treatment with ipilimumab, resulted in the identification of a set of potential biomarkers that were associated with occurrence of GI irAEs. However, because of the low sensitivity of these biomarkers, they cannot be used alone to predict which patients will develop GI irAEs. Further investigation of these biomarkers in a larger patient cohort is warranted.

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“…2A). As CD66 antigens may also be stored in cytoplasmic granules [43,44], we followed CD66 expression by Western blotting. In this analysis, small amounts of CD66c were found in untreated cells and decreased to undetectable amounts by Day 4, and CD66a and CD66d revealed an opposite expression profile (Fig.…”

Section: Differentiation Into Neutrophil Lineagementioning

confidence: 99%

Differential cell fates induced by all-trans retinoic acid-treated HL-60 human leukemia cells

Ozeki

Shively

2008

Journal of Leukocyte Biology

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HL-60 human leukemia cells, differentiated into a neutrophil lineage by all-trans retinoic acid (ATRA) treatment, express three members of the carcinoembryonic antigen (CEA) gene family, CEA-related cell adhesion molecule 1 (CEACAM1; CD66a), CEACAM3 (CD66d), and CEACAM6 (CD66c). CD66d is a neutrophil lineage-specific marker, and CD66a and CD66c are found on epithelial and other cells. HL-60 cells continuously treated with ATRA underwent apoptosis, and cells transiently treated for 1 day underwent cell-cycle arrest, entered into senescence, and exhibited reduced apoptosis with CD66-positive cells accounting for the majority of live cells. CD66 antigens were also induced in NB4 leukemic cells upon continuous treatment with ATRA. NB4 cells underwent apoptosis with a higher frequency in transient versus continuous-treated cells (38% vs. 19% at Day 5), in contrast to HL-60 cells that underwent cell-cycle arrest and senescence when transiently treated with ATRA. CD66 antigens were not induced in transient, ATRA-treated NB4 cells compared with HL-60 cells. Cell-cycle arrest in HL-60 cells involved reduction in expression levels of p21, cyclins D and E, while Rb1 exhibited reduction in protein levels without changes in mRNA levels over the time course of ATRA treatment. Analysis of several proapoptotic proteins implicated the activation of calpain and cleavage of Bax in the intrinsic apoptotic pathway, similar to published studies about the apoptosis of neutrophils. CD1d expression was also induced by ATRA in HL-60 cells and ligation with anti-CD1d antibody-induced apoptosis. In contrast, CD1d-positive primary monocytes were protected from spontaneous apoptosis by CD1d ligation. These studies demonstrate distinct cell fates for ATRA-treated HL-60 cells that provide new insights into ATRA-induced cell differentiation.

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Subcellular localization and mobilization of carcinoembryonic antigen‐related cell adhesion molecule 8 in human neutrophils

Cited by 18 publications

References 38 publications

Soluble CEACAM8 Interacts with CEACAM1 Inhibiting TLR2-Triggered Immune Responses

Soluble CEACAM8 Interacts with CEACAM1 Inhibiting TLR2-Triggered Immune Responses

Gene expression profiling of whole blood in ipilimumab-treated patients for identification of potential biomarkers of immune-related gastrointestinal adverse events

Differential cell fates induced by all-trans retinoic acid-treated HL-60 human leukemia cells

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