The effects of targeted deletion of cannabinoid receptors CB1 and CB2 on intranasal sensitization and challenge with adjuvant-free ovalbumin.
The mechanisms by which cannabinoid receptors CB(1) and CB(2) modulate immune function are not fully elucidated. Critical tools for the determination of the role of both receptors in the immune system are CB(1)/CB(2) double null mice (CB(1)/CB(2) null), and previous studies have shown that CB(1)/CB(2) null mice exhibit exaggerated responses to various immunological stimuli. The objective of these studies was to determine the magnitude to which CB(1)/CB(2) 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 CB(1)/CB(2) 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 CB(1)/CB(2) null mice, with exceptions being modest reductions in OVA-induced IgE and attenuation of BALF neutrophilia in CB(1)/CB(2) null mice as compared with wild-type mice. These results suggest that T-cell responses are not universally exaggerated in CB(1)/CB(2) null mice.
Kaplan
Barbara L F
BL
Center for Integrative Toxicology, Michigan State University, East Lansing, Michigan 48824, USA.
Lawver
Jody E
JE
Karmaus
Peer W F
PW
Ngaotepprutaram
Thitirat
T
Birmingham
Neil P
NP
Harkema
Jack R
JR
Kaminski
Norbert E
NE
D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000485:Allergens / Q000008:administration & dosage* / Q000276:immunology; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008168:Lung / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage* / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000276:Adjuvants, Immunologic; D000485:Allergens; D016207:Cytokines; D007074:Immunoglobulin G; D012333:RNA, Messenger; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D007073:Immunoglobulin E; D010047:Ovalbumin