title: Differential effect of CCL2 on constitutive neutrophil apoptosis between normal and asthmatic subjects.
abstract: In this study, we investigated the effects of CCL2 on constitutive apoptosis of normal and asthmatic neutrophils. CCL2 blocked the constitutive apoptosis of normal neutrophils through CCR2. CCL2 also induced elevation of the cytosolic Ca(2+) concentration but had no effect on normal neutrophil chemotaxis. Constitutive apoptosis, calcium influx, and cell migration of asthmatic neutrophils were not affected by CCL2 stimulation. Supernatant collected from CCL2-treated normal neutrophils inhibited the constitutive apoptosis of normal neutrophils. Anti-apoptotic signaling mediated by CCL2 was found to be associated with the PI3K/Akt/ERK/NF-κB cascade in normal neutrophils. Both the cleavage of procaspase 3 and procaspase 9 and the decrease of in Mcl-1 expression were delayed by CCL2 stimulation. Inhibition of NF-κB blocked constitutive apoptosis of neutrophils from asthmatic patients via inhibition of the cleavage of procaspase 3 and procaspase 9, in contrast to normal neutrophils. NF-κB was involved in CCL2-induced anti-apoptotic signaling in normal neutrophils, whereas NF-κB functioned as a basal pro-apoptotic factor in asthmatic neutrophils. A better understanding of the difference in the regulation of neutrophil apoptosis due to CCL2 between normal individuals and asthmatics will enable elucidation of the role of CC chemokine in neutrophils and a framework for understanding the pathogenesis of asthma.
authors: Department of Biomedical Laboratory Science, School of Medicine, Eulji University, Daejeon, Repulbic of Korea.
authors: Eun Ju
authors: EJ
authors: Yang
authors: Eugene
authors: E
authors: Choi
authors: Jesang
authors: J
authors: Ko
authors: Dong-Hee
authors: DH
authors: Kim
authors: Ji-Sook
authors: JS
authors: Lee
authors: In Sik
authors: IS
authors: Kim
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D001249:Asthma / Q000276:immunology* / Q000473:pathology; D016022:Case-Control Studies; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D054390:Receptors, CCR2 / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D055815:Young Adult
chemical_list: C111835:CCL2 protein, human; C515334:CCR2 protein, human; D018932:Chemokine CCL2; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D054390:Receptors, CCR2; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9