5-lipoxygenase-dependent recruitment of neutrophils and macrophages by eotaxin-stimulated murine eosinophils.
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.
Department of Immunology, IMPG, Universidade Federal do Rio de Janeiro, CCS, Bloco I, Room I-2-066, 21941-590 Rio de Janeiro, Brazil ; Department of Pediatrics, IFF, FIOCRUZ, 22250-020 Rio de Janeiro, Brazil.
Ricardo Alves
RA
Luz
Department of Immunology, IMPG, Universidade Federal do Rio de Janeiro, CCS, Bloco I, Room I-2-066, 21941-590 Rio de Janeiro, Brazil.
Pedro
P
Xavier-Elsas
Department of Pediatrics, IFF, FIOCRUZ, 22250-020 Rio de Janeiro, Brazil.
Bianca
B
de Luca
Department of Immunology, IMPG, Universidade Federal do Rio de Janeiro, CCS, Bloco I, Room I-2-066, 21941-590 Rio de Janeiro, Brazil.
Daniela
D
Masid-de-Brito
Department of Immunology, IMPG, Universidade Federal do Rio de Janeiro, CCS, Bloco I, Room I-2-066, 21941-590 Rio de Janeiro, Brazil.
Priscila Soares
PS
Cauduro
Department of Immunology, IMPG, Universidade Federal do Rio de Janeiro, CCS, Bloco I, Room I-2-066, 21941-590 Rio de Janeiro, Brazil.
Luiz Carlos Gondar
LC
Arcanjo
Department of Immunology, IMPG, Universidade Federal do Rio de Janeiro, CCS, Bloco I, Room I-2-066, 21941-590 Rio de Janeiro, Brazil.
Ana Carolina Cordeiro Faria
AC
dos Santos
Department of Medical Microbiology, IMPG, Universidade Federal do Rio de Janeiro, 21941-590 Rio de Janeiro, Brazil.
Ivi Cristina Maria
IC
de Oliveira
Department of Pediatrics, IFF, FIOCRUZ, 22250-020 Rio de Janeiro, Brazil.
Maria Ignez Capella
MI
Gaspar-Elsas
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D054413:Chemokine CCL11 / Q000737:chemistry*; D004804:Eosinophils / Q000166:cytology / Q000201:enzymology*; D004926:Escherichia coli / Q000378:metabolism; D005260:Female; D006098:Granulocytes / Q000166:cytology; D008264:Macrophages / Q000166:cytology / Q000201:enzymology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000166:cytology; D009154:Mutation; D009504:Neutrophils / Q000166:cytology / Q000201:enzymology*; D010587:Phagocytosis
D054413:Chemokine CCL11; D001094:Arachidonate 5-Lipoxygenase