Bactericidal activity of human eosinophilic granulocytes against Escherichia coli

Eosinophils participate in allergic inflammation and may have roles in the body's defense against helminthic infestation, Even under noninflammatory c onditions, eosinophils are present in the mucosa of the large intestine, wh ere large numbers of gram-negative bacteria reside. Therefore, roles for eo sinophils in host defenses against bacterial invasion are possible. In a sy stem for bacterial viable counts, the bactericidal activity of eosinophils and the contribution of different cellular antibacterial systems against Es cherichia coli,were investigated. Eosinophils showed a rapid and efficient killing off. coli under aerobic conditions, whereas under anaerobic conditi ons bacterial killing decreased dramatically. In addition, diphenylene iodo nium chloride (DPI), an inhibitor of the NADPH oxidase and thereby of super oxide production, also significantly inhibited bacterial killing. The inhib itor of nitric oxide (NO) production L-N-5-(1-iminoethyl)-ornithine dihydro chloride did not affect the killing efficiency, suggesting that NO or deriv atives thereof are of minor importance under the experimental conditions us ed. To investigate the involvement of superoxide and eosinophil peroxidase (EPO) in bacterial killing, EPO was blocked by azide, The rate of E, coli k illing decreased significantly in the presence of azide, whereas addition o f DPI did not further decrease the killing, suggesting that superoxide acts in conjunction,vith EPO. Bactericidal activity was seen in eosinophil extr acts containing granule proteins, indicating that oxygen-independent killin g may be of importance as well. The findings suggest that eosinophils can p articipate in host defense against gram-negative bacterial invasion and tha t oxygen-dependent killing, i.e., superoxide acting in conjunction with EPO , may be the most important bactericidal effector function of these cells.