Stem cell factor-induced leukotriene B-4 production cooperates with eotaxin to mediate the recruitment of eosinophils during allergic pleurisy in mice

The understanding of the mechanisms underlying eosinophil recruitment in vi vo may aid in the development of novel strategies for the treatment of alle rgic disorders. In this study, we investigated the role of chemokines in th e cascade of events leading to eosinophil recruitment in a stem cell factor (SCF)- and leukotriene B-4 (LTB4)-dependent allergic pleurisy model in mic e. The intrapleural administration of the eosinophil-active chemokines eota xin, RANTES, and macrophage-inflammatory protein la (MIP-1 alpha) induced a time- and dose-dependent eosinophil recruitment. Pretreatment with anti-eo taxin, but not anti-RANTES or anti-MIP-la, blocked the recruitment of eosin ophils following Ag challenge of sensitized animals, and significant eotaxi n immunoreactivity was detected in the pleural cavity of these animals. Sim ilarly, only the anti-eotaxin inhibited the eosinophil recruitment induced by injection of SCF in naive animals. However, blockade of SCF did not inhi bit the release of eotaxin after Ag challenge of sensitized mice. Akin to i ts effects on SCF and in the allergic reaction, eotaxin-induced eosinophil recruitment was blocked by the LTB4 receptor antagonist CP105696. Neverthel ess, SCF, but not eotaxin, appeared to regulate the endogenous release of L TB4 after Ag challenge. Finally, we show that low doses of eotaxin synergiz ed with LTB4 to induce eosinophil recruitment in the pleural cavity. Overal l, the present results show that eotaxin and SCF-induced LTB4 cooperate to induce eosinophil recruitment into sites of allergic inflammation. Cooperat ion between inflammatory mediators must be an important phenomenon in vivo, explaining both the ability of lower concentrations of mediators to induce a full-blown functional response and the effectiveness of different strate gies at inhibiting these responses. The Journal of Immunology, 2001.