Eosinophils from patients with asthma express higher levels of the pan‐leucocyte receptor CD45 and the isoform CD45RO

Blaylock, Morgan Graeme; Lipworth, Brian J.; Dempsey, Owen; Duncan, Clare; Lee, D. K. C.; Lawrie, A.; Douglas, J. G.; Walsh, Garry Michael

doi:10.1046/j.1365-2222.2003.01697.x

Cited by 13 publications

(9 citation statements)

References 24 publications

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“…36 The association results for the individual SNPs and for the haplotypes indicate that SFRS8 acts as a weak predisposing gene for asthma. When evaluating significant association studies, it is important to keep in mind that the literature reports numerous primary studies of significant associations but few associations have been reproduced.…”

Section: Discussionmentioning

confidence: 96%

Significant linkage to chromosome 12q24.32-q24.33 and identification of SFRS8 as a possible asthma susceptibility gene

Brasch‐Andersen

Tan

Børglum

et al. 2006

Thorax

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Section: Discussionmentioning

confidence: 96%

Significant linkage to chromosome 12q24.32-q24.33 and identification of SFRS8 as a possible asthma susceptibility gene

Brasch‐Andersen

Tan

Børglum

et al. 2006

Thorax

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“…The latter was constitutively expressed, unlike peripheral blood eosinophils, which require activation with cytokines including IL-3 and IL-5 before CD69 is expressed [32]. In contrast, CD95, CD45, and CD45 isoform expression by differentiated EoL-1 was comparable with that of resting peripheral blood eosinophils [30]. We found that differentiated EoL-1 had comparable levels of constitutive apoptosis with peripheral blood eosinophils and were sensitive to the apoptosis-inducing effects of mAb against CD45 and the isoforms CD45RA and CD45RB, CD69, or CD95.…”

Section: Discussionmentioning

confidence: 99%

Membrane receptor-mediated apoptosis and caspase activation in the differentiated EoL-1 eosinophilic cell line

Al-Rabia

Blaylock

Sexton

et al. 2004

Journal of Leukocyte Biology

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Caspases are key molecules in the control of apoptosis, but relatively little is known about their contribution to eosinophil apoptosis. We examined caspase-3, -8, and -9 activities in receptor ligation-dependent apoptosis induction in the differentiated human eosinophilic cell line EoL-1. Differentiated EoL-1 exhibited bi-lobed nuclei, eosinophil-associated membrane receptors, and basic granule proteins. Annexin-V fluorescein isothiocyanate binding to EoL-1 revealed significant (P<0.01) apoptosis induction in cells cultured for 20 h with monoclonal antibodies (mAb) specific for CD45 (71%+/-4.3), CD45RA (58%+/-2.3), CD45RB (68%+/-2.4), CD95 (47%+/-2.6), and CD69 (52%+/-2.1) compared with control (23%+/-1.6) or CD45RO mAb (27%+/-3.9). The pan-caspase inhibitor Z-Val-Ala-Asp-fluoromethylketone (fmk) and inhibitors of caspase-8 (Z-Ile-Glu-Thr-Asp-fmk) and caspase-9 (Z-Leu-Glu-His-Asp-fmk) significantly inhibited mAb-induced apoptosis of EoL-1 but had no effect on constitutive (baseline) apoptosis at 16 and 20 h. Caspase activity was analyzed using the novel CaspaTag trade mark technique and flow cytometry. EoL-1 treated with pan-CD45, CD45RA, CD45RB, and CD95 mAb exhibited caspase-3 and -9 activation at 12 h post-treatment, which increased at 16 and 20 h. Activated caspase-8 was detected 12 and 16 h after ligation with CD45, CD45RA, CD45RB, and CD95 mAb followed by a trend toward basal levels at 20 h. CD69 ligation resulted in caspase-3 activation, a modest but significant activation of caspase-8, and a loss in mitochondrial transmembrane potential but had no significant effect on activation of caspase-9. Thus, the intrinsic and extrinsic caspase pathways are involved in controlling receptor ligation-mediated apoptosis induction in human eosinophils, findings that may aid the development of a more targeted, anti-inflammatory therapy for asthma.

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“…As such, it has also been demonstrated that the absence of CD45 may result in severe combined immunodeficiency (28). CD45 may be expressed by all leucocytes, including eosinophils (29), which have been implicated as effector cells in asthma and other allergic diseases (30). In asthma, eosinophils and their secreted mediators are believed to be a major contributor to the inflammation underlying the pathophysiological changes in the airways (31).…”

Section: Discussionmentioning

confidence: 99%

Microarray data analysis to identify differentially expressed genes and biological pathways associated with asthma

Liu

Huang

et al. 2018

Exp Ther Med

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The present study aimed to identify differentially expressed genes (DEGs) and biological processes (BPs) associated with asthma. DEGs between allergic asthma and healthy controls were screened from GSE15823. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using Database for Annotation, Visualization and Integrated Discovery. A protein-protein interaction network was constructed, followed by module mining and functional analysis. Additionally, GSE41649 was downloaded to validate the reliability of the results. In GSE41649, DEGs were identified and compared with key DEGs identified in GSE15823. A total of 43 upregulated and 275 downregulated DEGs were obtained from GSE15823. Upregulated DEGs, such as nitric oxide synthase 2 (NOS2), were enriched in BPs related to oxidation reduction. Downregulated DEGs, such as chemokine (C-C motif) ligand 19 (CCL21) and Cys-X-Cys ligand (CXCL9), were enriched in immune response-related BPs. Protein tyrosine phosphatase receptor type C (PTPRC), CCL21, and CXCL9 were identified as hub genes. The DEGs in module 1 were significantly involved in the chemokine signaling pathway (P<0.05). The expression of the key genes obtained in GSE15823 demonstrated the same variation directions in the two datasets. The immune response, oxidants and nitric oxide metabolic pathways may have important roles in the progression of asthma. DEGs of PTPRC, CCL21, CXCL9 and NOS2 may be the potential targets for asthma diagnosis and treatment.

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Eosinophils from patients with asthma express higher levels of the pan‐leucocyte receptor CD45 and the isoform CD45RO

Abstract: Higher expression of CD45 and CD45RO by eosinophils from asthmatic patients appeared to be a consequence of asthma rather than atopy and further supports a role for activated eosinophils in asthma.

Cited by 13 publications

References 24 publications

Significant linkage to chromosome 12q24.32-q24.33 and identification of SFRS8 as a possible asthma susceptibility gene

Significant linkage to chromosome 12q24.32-q24.33 and identification of SFRS8 as a possible asthma susceptibility gene

Membrane receptor-mediated apoptosis and caspase activation in the differentiated EoL-1 eosinophilic cell line

Microarray data analysis to identify differentially expressed genes and biological pathways associated with asthma

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