Increased progenitor cell proliferation in the peripheral blood of patients with bronchial asthma: The role of nitric oxide

Background: Asthma exacerbation is associated with increased numbers of cir culating CD34(+) progenitor cells, which may migrate to airways and develop into mature cells under the effects of cytokines and hematopoietic factors . Nitric oxide (NO) generation is enhanced in asthma and is known to suppre ss human hematopoiesis. Objectives: We studied circulating progenitor cells in the blood of patient s with varying severity of asthma and examined the contribution of NO to th eir proliferation into eosinophil-forming colonies ex vivo, Methods: With use of multiparameter flow cytometric analyses, the cell numb ers and intracellular inducible NO synthase (iNOS) immunoreactivity of circ ulating CD34(+) cells in peripheral blood was measured. The serum level of GM-CSF or IL-5 was also determined, The colonies grown from progenitor cell s were cultured in methylcellulose either in the presence or absence of gro wth factors, including GM-CSF, stem cell factor, and IL-3. Results: A significantly greater number of circulating CD34(+) cells increa sed together with higher intracellular iNOS immunoreactivity in moderate as thmatics compared with mild intermittent asthmatics and healthy subjects. T here was no significant difference in iNOS immunoreactivities or CD34(+) pr ogenitor cell numbers between healthy subjects and those with mild intermit tent asthma. Serum levels of GM-CSF or IL-5 mere significantly higher in al l asthmatics compared with healthy subjects and correlated with circulating CD34+ cells. A greater number of colonies was grown either in the presence or absence of growth factors with a higher percentage of cells of eosinoph il lineage in asthmatics than in health subjects. N-G-nitro-L-arginine meth yl ester potentiated and sodium nitroprusside inhibited the colony growth i n both asthmatic and healthy subjects without a significant change in the p ercentage of eosinophil lineage, Conclusions: The production of NO from progenitor cells or other circulatin g cells may act in an autocrine or paracrine fashion to regulate progenitor cell growth and colony formation. However, this is not sufficient to contr ol the increased proliferation of progenitor cells observed in asthma.