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Differential effect of CCL2 on constitutive neutrophil apoptosis between normal and asthmatic subjects
Author(s) -
Yang Eun Ju,
Choi Eugene,
Ko Jesang,
Kim DongHee,
Lee JiSook,
Kim In Sik
Publication year - 2012
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.22995
Subject(s) - apoptosis , chemotaxis , ccl2 , chemokine , interleukin 8 , immunology , chemistry , microbiology and biotechnology , biology , inflammation , medicine , receptor , biochemistry
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. J. Cell. Physiol. 227: 2567–2577, 2012. © 2011 Wiley Periodicals, Inc.