The Effects of Targeted Deletion of Cannabinoid Receptors CB1 and CB2 on Intranasal Sensitization and Challenge with Adjuvant-free Ovalbumin

• Published in: Toxicologic pathology Vol. 38; no. 3; pp. 382 - 392
• Main Authors: Kaplan, Barbara L. F., Lawver, Jody E., Karmaus, Peer W. F., Ngaotepprutaram, Thitirat, Birmingham, Neil P., Harkema, Jack R., Kaminski, Norbert E.
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01-04-2010; Sage Publications
• Subjects: Adjuvants, Immunologic; Administration, Intranasal; Allergens - administration & dosage; Allergens - immunology; Animals; Biological and medical sciences; Bronchial Hyperreactivity - genetics; Bronchial Hyperreactivity - immunology; Bronchial Hyperreactivity - metabolism; Bronchoalveolar Lavage Fluid - immunology; Cytokines - biosynthesis; Drug addictions; Enzyme-Linked Immunosorbent Assay; Female; Immunoglobulin E - blood; Immunoglobulin G - blood; Lung - immunology; Lung - metabolism; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Ovalbumin - administration & dosage; Ovalbumin - immunology; Receptor, Cannabinoid, CB1 - genetics; Receptor, Cannabinoid, CB1 - immunology; Receptor, Cannabinoid, CB1 - metabolism; Receptor, Cannabinoid, CB2 - genetics; Receptor, Cannabinoid, CB2 - immunology; Receptor, Cannabinoid, CB2 - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Toxicology; allergic airway hyperresponsiveness; CB2; CB1; inflammation; cannabinoid; CB1 cannabinoid receptor; Immunopathology; Allergy; Ovalbumin; Targeting; Hyperreactivity; Toxicity; Inflammation; Intranasal administration; Cannabinoid; Respiratory system; Respiratory tract; Target; Cannabinoid receptor; Deletion; Adjuvant; Sensitization; Drug of abuse; CB
• ISSN: 0192-6233; 1533-1601
• DOI: 10.1177/0192623310362706

The mechanisms by which cannabinoid receptors CB1 and CB2 modulate immune function are not fully elucidated. Critical tools for the determination of the role of both receptors in the immune system are CB1/CB2 double null mice (CB1/CB2 null), and previous studies have shown that CB1/CB2 null mice exhibit exaggerated responses to various immunological stimuli. The objective of these studies was to determine the magnitude to which CB1/CB2 null mice responded to the respiratory allergen ovalbumin (OVA) as compared with wild-type C57BL/6 mice. The authors determined that in the absence of adjuvant, both wild-type and CB1/CB2 null mice mounted a marked response to intranasally instilled OVA as assessed by inflammatory cell infiltrate in the bronchoalveolar lavage fluid (BALF), eosinophilia, induction of mucous cell metaplasia, and IgE production. Many of the endpoints measured in response to OVA were similar in wild-type versus CB1/CB2 null mice, with exceptions being modest reductions in OVA-induced IgE and attenuation of BALF neutrophilia in CB1/CB2 null mice as compared with wild-type mice. These results suggest that T-cell responses are not universally exaggerated in CB1/CB2 null mice.