The Deficiency of PGI 2 Signaling Induces STAT6-independent Allergic Airway Inflammation

Abstract

S A T U R D A Y 209 Peripheral Blood Natural Killer Cells from Asthmatic Subjects Respond Differently to Stimulation with Poly(I:C) and Diesel Exhaust Particles C. V. E. Chehrazi, K. M. Horvath, I. Jaspers; University of North Carolina, Chapel Hill, NC. RATIONALE: It has been suggested that NK cells in asthmatic and healthy subjects differ, but it is unknown whether these differences alter NK responses to virus and contribute to increased asthmatic susceptibility to viral infections. Data from our lab suggest that diesel exhaust exposure enhances virally-induced exacerbation of allergic inflammation, yet the role of NK cells in these responses is unknown; therefore, we examined the response of asthmatic peripheral NK cells to polyriboinosinic acid-polyribocytidylic acid [poly(I:C)a mimetic of virus-derived dsRNA] and diesel exhaust particles (DEP). METHODS: NK cells were isolated from the blood of asthmatic subjects and subsequently incubated with vehicle, poly(I:C), DEP, or poly (I:C)+DEP. Flow cytometry and cytokine analysis were performed to evaluate changes in cell surface markers and mediator profiles, respectively. RESULTS: As compared to vehicle control, poly(I:C) and DEP stimulation significantly augmented surface expression of CD16, which mediates antibody-dependent cell-mediated cytotoxicity. In contrast, only DEP stimulation significantly enhanced surface expression of CXCR3, the receptor for CXCL10, which is expressed by virally-infected cells and promotes NK chemotaxis. Analysis of cytokines and other cell surface receptors will be performed. CONCLUSIONS: Stimulation with poly(I:C) and DEP alters the expression of cell surface markers involved in NK activity. Whereas NK cytotoxicity appears enhanced by stimulation with dsRNA, NK chemotactic potential appears enhanced by DEP, suggesting that the NK response of asthmatics may be altered by air pollution. These novel findings offer insight into potential mechanisms by which pollutant exposure amplifies asthmatic morbidity due to viral infection.