Role of CCL21 and CCL19 in allergic inflammation in the ovalbumin-specific murine asthmatic model.

Abstract

BACKGROUND:

Dendritic cells are the most powerful of the antigen-presenting cells and are known to play important roles in sensitization and inflammation in allergen-specific asthma. Various cytokines and chemokines are involved in the maturation and activation of dendritic cells. Among them is CC chemokine ligand (CCL)21, a key chemokine in the entry of naive T cells and antigen-stimulated dendritic cells into the T-cell zones of secondary lymphoid organs, which is a critical process in antigen-specific T-cell activation.

OBJECTIVE:

We studied the role of CCL21 in airway inflammation in asthma by using BALB/c-plt/plt (plt) mice, which possess genetic defects in expression of both CCL21 and CCL19.

METHODS:

Plt and control BALB/c mice were immunized with ovalbumin and alum 4 times and thereafter were subjected to a 2-week regimen of ovalbumin inhalation.

RESULTS:

In plt mice, ovalbumin-specific IgE response was delayed compared with control BALB/c mice, but they had the same level of response after final immunization. Although airway inflammation and response to acetylcholine were significantly reduced compared with BALB/c mice, significant eosinophilic inflammation and hyperresponsiveness were also observed in plt mice after 2 weeks of inhalation. Four weeks after cessation of inhalation, airway inflammation and hyperresponsiveness in plt mice were greater than in BALB/c mice. At the time of resolution of airway inflammation, IL-10 production was enhanced in BALB/c mice but not in plt mice.

CONCLUSION:

The chemokines CCL21 and CCL19 were critical for resolution of airway inflammation.

CLINICAL IMPLICATIONS:

The findings about the chemokines for induction and resolution of inflammation are key to establishing a new strategy for asthma immunotherapy.

• Authors: Naomi Yamashita, Hiroyuki Tashimo, Yukiko Matsuo, Hirofumi Ishida, Kenta Yoshiura, Katsuaki Sato, Naohide Yamashita, Terutaka Kakiuchi, Ken Ohta
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 117 Issue 5 Pg. 1040-6 (May 2006) ISSN: 0091-6749 [Print] United States
• PMID: 16675330 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CCL19 protein, human
• CCL21 protein, human
• CCR7 protein, human
• Ccl19 protein, mouse
• Ccl21c protein, mouse
• Ccr7 protein, mouse
• Chemokine CCL19
• Chemokine CCL21
• Chemokines, CC
• Epitopes, T-Lymphocyte
• Immunoglobulin G
• Inflammation Mediators
• Receptors, CCR7
• Receptors, Chemokine
• Receptors, Interleukin-2
• Immunoglobulin E
• Ovalbumin

Topics

• Animals
• Asthma (genetics, immunology, metabolism)
• Bronchial Hyperreactivity (immunology, pathology)
• Chemokine CCL19
• Chemokine CCL21
• Chemokines, CC (deficiency, genetics, physiology)
• Disease Models, Animal
• Epitopes, T-Lymphocyte (genetics, immunology)
• Humans
• Hypersensitivity (genetics, immunology, pathology)
• Immunoglobulin E (biosynthesis)
• Immunoglobulin G (biosynthesis)
• Inflammation (immunology, metabolism, pathology)
• Inflammation Mediators (administration & dosage, physiology)
• Lymph Nodes (abnormalities, metabolism, pathology)
• Mice
• Mice, Inbred BALB C
• Mice, Mutant Strains
• Ovalbumin (immunology)
• Receptors, CCR7
• Receptors, Chemokine (biosynthesis, genetics)
• Receptors, Interleukin-2 (biosynthesis, genetics)