CCL7 and CXCL10 orchestrate oxidative stress-induced neutrophilic lung inflammation

L. Michalec, Barun Choudhury, E. Postlethwait, J. S. Wild, R. Alam, M. Lett-Brown, Sanjiv Sur

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Abstract

Oxidative stress from ozone (O3) exposure augments airway neutrophil recruitment and chemokine production. We and others have shown that severe and sudden asthma is associated with airway neutrophilia, and that O3 oxidative stress is likely to augment neutrophilic airway inflammation in severe asthma. However, very little is known about chemokines that orchestrate oxidative stress-induced neutrophilic airway inflammation in vivo. To identify these chemokines, three groups of BALB/c mice were exposed to sham air, 0.2 ppm O3, or 0.8 ppm O3 for 6 h. Compared with sham air, 0.8 ppm O3, but not 0.2 ppm O3, induced pronounced neutrophilic airway inflammation that peaked at 18 h postexposure. The 0.8 ppm O3 up-regulated lung mRNA of CXCL1,2,3 (mouse growth-related oncogene-α and macrophage-inflammatory protein-2), CXCL10 (IFN-γ-inducible protein-10), CCL3 (macrophage-inflammatory protein-1α), CCL7 (monocyte chemoattractant protein-3), and CCL11 (eotaxin) at 0 h postexposure, and expression of CXCL10, CCL3, and CCL7 mRNA was sustained 18 h postexposure. O3 increased lung protein levels of CXCL10, CCL7, and CCR3 (CCL7R). The airway epithelium was identified as a source of CCL7. The role of up-regulated chemokines was determined by administering control IgG or IgG Abs against six murine chemokines before O3 exposure. As expected, anti-mouse growth-related oncogene-α inhibited neutrophil recruitment. Surprisingly, Abs to CCL7 and CXCL10 also decreased neutrophil recruitment by 63 and 72%, respectively. These findings indicate that CCL7 and CXCL10, two chemokines not previously reported to orchestrate neutrophilic inflammation, play a critical role in mediating oxidative stress-induced neutrophilic airway inflammation. These observations may have relevance in induction of neutrophilia in severe asthma.

Original languageEnglish (US)
Pages (from-to)846-852
Number of pages7
JournalJournal of Immunology
Volume168
Issue number2
StatePublished - Jan 15 2002

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Chemokines
Pneumonia
Oxidative Stress
Neutrophil Infiltration
Inflammation
Asthma
Oncogenes
Chemokine CCL7
Immunoglobulin G
Air
Chemokine CXCL10
Chemokine CXCL2
Macrophage Inflammatory Proteins
Lung
Messenger RNA
Ozone
Growth
Proteins
Epithelium

ASJC Scopus subject areas

  • Immunology

Cite this

Michalec, L., Choudhury, B., Postlethwait, E., Wild, J. S., Alam, R., Lett-Brown, M., & Sur, S. (2002). CCL7 and CXCL10 orchestrate oxidative stress-induced neutrophilic lung inflammation. Journal of Immunology, 168(2), 846-852.

CCL7 and CXCL10 orchestrate oxidative stress-induced neutrophilic lung inflammation. / Michalec, L.; Choudhury, Barun; Postlethwait, E.; Wild, J. S.; Alam, R.; Lett-Brown, M.; Sur, Sanjiv.

In: Journal of Immunology, Vol. 168, No. 2, 15.01.2002, p. 846-852.

Research output: Contribution to journalArticle

Michalec, L, Choudhury, B, Postlethwait, E, Wild, JS, Alam, R, Lett-Brown, M & Sur, S 2002, 'CCL7 and CXCL10 orchestrate oxidative stress-induced neutrophilic lung inflammation', Journal of Immunology, vol. 168, no. 2, pp. 846-852.
Michalec L, Choudhury B, Postlethwait E, Wild JS, Alam R, Lett-Brown M et al. CCL7 and CXCL10 orchestrate oxidative stress-induced neutrophilic lung inflammation. Journal of Immunology. 2002 Jan 15;168(2):846-852.
Michalec, L. ; Choudhury, Barun ; Postlethwait, E. ; Wild, J. S. ; Alam, R. ; Lett-Brown, M. ; Sur, Sanjiv. / CCL7 and CXCL10 orchestrate oxidative stress-induced neutrophilic lung inflammation. In: Journal of Immunology. 2002 ; Vol. 168, No. 2. pp. 846-852.
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abstract = "Oxidative stress from ozone (O3) exposure augments airway neutrophil recruitment and chemokine production. We and others have shown that severe and sudden asthma is associated with airway neutrophilia, and that O3 oxidative stress is likely to augment neutrophilic airway inflammation in severe asthma. However, very little is known about chemokines that orchestrate oxidative stress-induced neutrophilic airway inflammation in vivo. To identify these chemokines, three groups of BALB/c mice were exposed to sham air, 0.2 ppm O3, or 0.8 ppm O3 for 6 h. Compared with sham air, 0.8 ppm O3, but not 0.2 ppm O3, induced pronounced neutrophilic airway inflammation that peaked at 18 h postexposure. The 0.8 ppm O3 up-regulated lung mRNA of CXCL1,2,3 (mouse growth-related oncogene-α and macrophage-inflammatory protein-2), CXCL10 (IFN-γ-inducible protein-10), CCL3 (macrophage-inflammatory protein-1α), CCL7 (monocyte chemoattractant protein-3), and CCL11 (eotaxin) at 0 h postexposure, and expression of CXCL10, CCL3, and CCL7 mRNA was sustained 18 h postexposure. O3 increased lung protein levels of CXCL10, CCL7, and CCR3 (CCL7R). The airway epithelium was identified as a source of CCL7. The role of up-regulated chemokines was determined by administering control IgG or IgG Abs against six murine chemokines before O3 exposure. As expected, anti-mouse growth-related oncogene-α inhibited neutrophil recruitment. Surprisingly, Abs to CCL7 and CXCL10 also decreased neutrophil recruitment by 63 and 72{\%}, respectively. These findings indicate that CCL7 and CXCL10, two chemokines not previously reported to orchestrate neutrophilic inflammation, play a critical role in mediating oxidative stress-induced neutrophilic airway inflammation. These observations may have relevance in induction of neutrophilia in severe asthma.",
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