Immunostimulatory DNA mediates inhibition of eosinophilic inflammation and airway hyperreactivity independent of natural killer cells in vivo.
BACKGROUND
Immunostimulatory DNA sequences (ISS) inhibit eosinophilic inflammation and airway hyperreactivity in mouse models of asthma. In vitro ISS activate natural killer (NK) cells to secrete IFN-gamma, and this cytokine is hypothesized to contribute to the antiallergic effect of ISS in vivo.


OBJECTIVE
We investigated whether ISS activation of NK cells is important in mediating the reduction in airway hyperreactivity and the antieosinophilic effect of ISS in vivo.


METHODS
We assessed whether ISS modulated the development of eosinophilic airway inflammation and airway hyperreactivity to methacholine in ovalbumin (OVA)-sensitized and OVA allergen-challenged mice pretreated with an antibody to deplete NK cells.


RESULTS
Mice sensitized and challenged with OVA had significant bronchoalveolar lavage and lung eosinophilia, as well as airway hyperresponsiveness. ISS induced significant inhibition of bronchoalveolar lavage and lung eosinophilia, as well as airway hyperresponsiveness, in OVA-sensitized mice pretreated before OVA challenge with an NK cell-depleting antibody (NK(-) mice), as well as in mice pretreated with a control non-NK cell-depleting antibody (NK(+) mice). The NK cell-depleting antibody inhibited ISS-induced IFN-gamma production by spleen cells.


CONCLUSIONS
These studies demonstrate that depletion of NK cells has no significant effect on ISS-mediated inhibition of airway eosinophilia and airway hyperresponsiveness in vivo, suggesting that non-NK cells and cytokines other than IFN-gamma derived from NK cells mediate the majority of the ISS-inhibitory effect on eosinophilic inflammation and airway hyperresponsiveness in vivo.
Broide
D H
DH
Department of Medicine, University of California, San Diego, La Jolla 92093-0635, USA.
Stachnick
G
G
Castaneda
D
D
Nayar
J
J
Miller
M
M
Cho
J
J
Rodriquez
M
M
Roman
M
M
Raz
E
E
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D001855:Bone Marrow Diseases / Q000188:drug therapy / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D016085:Bronchoconstrictor Agents; D002478:Cells, Cultured; D004247:DNA / Q000627:therapeutic use*; D004802:Eosinophilia / Q000188:drug therapy / Q000276:immunology; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology*; D008212:Lymphocyte Depletion; D016210:Methacholine Chloride; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D011657:Pulmonary Eosinophilia / Q000188:drug therapy* / Q000276:immunology
D000276:Adjuvants, Immunologic; D016085:Bronchoconstrictor Agents; D016210:Methacholine Chloride; D007371:Interferon-gamma; D010047:Ovalbumin; D004247:DNA