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5-LIPOXYGENASE-DEPENDENT RECRUITMENT OF NEUTROPHILS AND MACROPHAGES BY EOTAXIN-STIMULATED MURINE EOSINOPHILS
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The roles of eosinophils in antimicrobial defense remain incompletely understood. In ovalbumin-sensitized mice, eosinophils are
selectively recruited to the peritoneal cavity by antigen, eotaxin, or leukotriene(LT)B4, a 5-lipoxygenase (5-LO) metabolite. 5-LO
blockade prevents responses to both antigen and eotaxin.We examined responses to eotaxin in the absence of sensitization and their
dependence on 5-LO. BALB/c or PAS mice and their mutants (5-LO-deficient ALOX; eosinophil-deficient GATA-1) were injected
i.p. with eotaxin, eosinophils, or both, and leukocyte accumulation was quantified up to 24 h. Significant recruitment of eosinophils
by eotaxin in BALB/c, up to 24 h, was accompanied bymuch larger numbers of recruited neutrophils andmonocytes/macrophages.
These effects were abolished by eotaxin neutralization and 5-LO-activating protein inhibitor MK886. In ALOX (but not PAS)
mice, eotaxin recruitment was abolished for eosinophils and halved for neutrophils. In GATA-1 mutants, eotaxin recruited neither
neutrophils nor macrophages. Transfer of eosinophils cultured from bone-marrow of BALB/c donors, or from ALOX donors, into
GATA-1 mutant recipients, i.p., restored eotaxin recruitment of neutrophils and showed that the critical step dependent on 5-LO is
the initial recruitment of eosinophils by eotaxin, not the secondary neutrophil accumulation. Eosinophil-dependent recruitment
of neutrophils in naive BALB/c mice was associated with increased binding of bacteria.
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