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

Abstract

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.

Inhibition of 5-lipoxygenase alleviates graft-versus-host disease

“…Supporting our hypothesis, the study published by Li et al (2014) showed that 5-LO inhibition improved acute liver failure, and that was associated with reduced macrophage number. Another study by Luz et al (2014) supports our findings of reduced macrophage infiltration in the intestine and liver of both 5-LO–deficient, leukocyte-transplanted mice and zileuton-treated mice. These authors showed that 5-LO inhibition by MK886 reduced recruitment of neutrophils and macrophages into the peritoneal cavity of mice stimulated with eotaxin, demonstrating the importance of the 5-LO pathway for the recruitment of those cells.…”

Falcarinol Is a Potent Inducer of Heme Oxygenase‐1 and Was More Effective than Sulforaphane in Attenuating Intestinal Inflammation at Diet‐Achievable Doses

“…Eosinophils are the first immune cells to be recruited to the site of injury in response to locally produced eotaxin, and are followed by more numerous neutrophils and macrophages [ 73 ]. As shown in Figure 8 , eotaxin increased 5.4-fold for LPS alone ( p < 0.001, PC) and it was attenuated with FA, which only showed a 4.1-fold increase ( p < 0.01), but not with SF (5.0-fold, p < 0.001) demonstrating that FA was able to show some protective effects in the initial phases of the LPS response.…”

Blockage of Eosinopoiesis by IL‐17A Is Prevented by Cytokine and Lipid Mediators of Allergic Inflammation

“…Male and female BALB/c mice, wild-type ones, and mutants lacking either IL-4 (IL-4 KO; Jackson Laboratory online reference http://jaxmice.jax.org/strain/002496.html ) functional genes or an enhancer element in the promoter region of gene coding for the GATA-1 transcription factor [ 26 ], required for eosinophil-lineage determination (GATA-1 dbl KO or GATA-1 for short; Jackson Laboratory online reference http://jaxmice.jax.org/strain/005653.html ), and C57BL/6 mice, wild-type ones, and mutants lacking iNOS [ 33 , Jackson reference #002596] functional genes were bred at CECAL-FIOCRUZ (Rio de Janeiro, Brazil) and used at 6–8 weeks of age. Animal housing and handling followed procedures approved by the Institutional Committee on Ethical Handling of Laboratory Animals (Licenses CEUA #L002-09; CEUA-CCS-UFRJ #181-13).…”

“…IL-17A regulates granulocyte populations by coupling granulocyte clearance from tissues to neutropoiesis in bone-marrow through induction of the granulocyte colony-stimulating factor (G-CSF) [ 24 ]. By contrast, less is known about IL-17A effects on eosinophils, which are closely related to neutrophils [ 25 ] but remain better known for their pathogenetic roles in allergy than for their contributions to antimicrobial defences [ 26 ].…”