5-Lipoxygenase-Dependent Recruitment of Neutrophils and Macrophages by Eotaxin-Stimulated Murine Eosinophils

Abstract EN

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 by much larger numbers of recruited neutrophils and monocytes/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.