Fig. 7: Prospective mechanisms of cigarette smoke-mediated IgA inhibition in the upper respiratory tract.

Mice exposed to cigarette smoke during the course of intranasal immunization with LPS/OVA demonstrated reduced induction of antigen (OVA)-specific IgA antibodies in the nasal and systemic circulation. These antibodies demonstrate reduced polyclonal avidity during the acute post-immunization period. (1) Evidence of impaired OVA-IgA ASC accumulation in the nasal mucosa, secondary lymphoid tissues, and bloodstream suggest an impairment in the activation these cells. Nasal OVA-IgA ASCs from smoke-exposed mice also demonstrate reduced OVA-binding capacity, suggesting that they possess a reduced antigen-binding affinity compared to room air controls. (2) Data also demonstrate that cigarette smoke exposure compromises the upregulation of VCAM-1 in the nasal mucosa following LPS exposure, suggesting that following generation in secondary lymphoid tissues, these cells may not be able to efficiently extravasate back into the nasal mucosa. (3) Finally, pIgR expression in the nasal mucosa was similarly impaired following immunization, strongly suggesting that IgA transepithelial transport may also be attenuated.