Effect of eosinophil cationic protein (ECP) on Hodgkin lymphoma cell lines

Lima

et al. 2012

DNA and Cell Biology

The eosinophil cationic protein (ECP) is a small polypeptide that originates from activated eosinophil granulocytes. A wide range of stimuli has been shown to induce the secretion of ECP. The gene that encodes the human ECP is located on chromosome 14, and the protein shares the overall three-dimensional structure and the RNase active-site residues with other proteins in the RNase A superfamily. Several single-nucleotide polymorphisms in the human ECP gene have been currently described. ECP has many biological functions, including an immunoregulatory function, the regulation of fibroblast activity, and the induction of mucus secretion in the airway. Additionally, the protein is a potent cytotoxic molecule and has the capacity to kill mammalian and nonmammalian cells. The purpose of this article was to review the known biological and genetic characteristics of ECP that contribute to the understanding of this protein's role in the development and progression of a wide variety of diseases.

Section: Biological Activitiesmentioning

confidence: 98%

Section: Biological Activitiesmentioning

confidence: 98%

Section: Biological Activitiesmentioning

confidence: 99%

mentioning

confidence: 97%

See 2 more Smart Citations

Eosinophil Cationic Protein: Overview of Biological and Genetic Features

Lima

et al. 2012

DNA and Cell Biology

“…Recent genotyping data on Hodgkin lymphoma patients linked the Arg97 polymorphism with a higher tumor eosinophilia, suggesting that a higher protein toxicity further triggered the eosinophil recruitment at the tumor . On the other hand, ECP glycosylation level was correlated to the protein cytotoxicity on several cancer cell lines , where partial carbohydrate removal increased the protein activity . Glycosylation, however, did not alter other protein properties such as skin lesions or RNase catalytic activities .…”

Section: Introductionmentioning

confidence: 98%

Protein post‐translational modification in host defense: the antimicrobial mechanism of action of human eosinophil cationic protein native forms

et al. 2014

Self Cite

Knowledge on the contribution of protein glycosylation in host defense antimicrobial peptides is still scarce. We have studied here how the posttranslational modification pattern modulates the antimicrobial activity of one of the best characterized leukocyte granule proteins. The human eosinophil cationic protein (ECP), an eosinophil specific granule protein secreted during inflammation and infection, can target a wide variety of pathogens. Previous work in human eosinophil extracts identified several ECP native forms and glycosylation heterogeneity was found to contribute to the protein biological properties. In this study we analyze for the first time the antimicrobial activity of the distinct native proteins purified from healthy donor blood. Low and heavy molecular weight forms were tested on Escherichia coli cell cultures and compared with the recombinant non-glycosylated protein. Further analysis on model membranes provided an insight towards an understanding of the protein behavior at the cytoplasmic membrane level. The results highlight the significant reduction in protein toxicity and bacteria agglutination activity for heavy glycosylated fractions. Notwithstanding, the lower glycosylated fraction mostly retains the lipopolysaccharide binding affinity together with the cytoplasmic membrane depolarization and membrane leakage activities. From structural analysis we propose that heavy glycosylation interferes with the protein self-aggregation, hindering the cell agglutination and membrane disruption processes. The results suggest the contribution of post-translational modifications to the antimicrobial role of ECP in host defense.

Eosinophilia in routine blood samples and the subsequent risk of hematological malignancies and death

et al. 2013

Eosinophilia may represent an early paraclinical sign of hematological malignant disease, but no reports exist on its predictive value for hematological malignancies. From the Copenhagen Primary Care Differential Count (CopDiff) Database, we identified 356,196 individuals with at least one differential cell count (DIFF) encompassing the eosinophil count during 2000-2007. From these, one DIFF was randomly chosen and categorized according to no (<0.5 3 10 9 /L), mild (0.5-1.0 3 10 9 /L) or severe (1.0 3 10 9 /L) eosinophilia. From the Danish Cancer Registry and the Danish Civil Registration System, we ascertained hematological malignancies and death within 3 years following the DIFF. Using multivariable logistic regression odds ratios (ORs) were calculated and adjusted for previous eosinophilia in a DIFF, sex, age, year, month, C-reactive protein, previous cancer, and comorbidity. ORs for developing Hodgkin's lymphoma (HL) was significantly increased in individuals exhibiting severe eosinophilia, OR 5 9.09 (C.I. 2.77-29.84), P 5 0.0003. The association with classical myeloproliferative neoplasms (cMPNs) showed an increasing risk with OR 5 1.65 (1.04-2.61) P 5 0.0322 and OR 5 3.87 (1.67-8.96) P 5 0.0016 for mild and severe eosinophilia. Eosinophilia was in a similar fashion associated with chronic lymphatic leukemia (CLL), OR 5 2.57 (1.50-4.43), P 5 0.0006 and OR 5 5.00 (1.57-15.94), P 5 0.0065, and all-cause death, OR of 1.16 (1.09-1.24), P < 0.0001 and 1.60 (1.35-1.91), P < 0.0001. We confirm associations between eosinophilia and HL and cMPNs, and in addition for the first time demonstrate a dose-dependent association between eosinophilia and CLL as well as death. Unexplained eosinophilia should prompt clinicians to consider conditions where early diagnosis may improve prognosis. Am.