Impact of MK886 on eosinophil counts and phenotypic features in toxocariasis.
Experimental toxocariasis was used as a model of eosinophil migration. Mice inoculated with 200 Toxocara canis eggs were treated with the leukotriene inhibitor MK886 (1 mg/kg/day). Eosinophils were counted in peripheral blood (PB), peritoneal cavity (PC) and bronchoalveolar lavage fluid (BALF) samples on post-infection days 3, 6, 12, 18, 24 and 36. Eosinophil expression of Mac-1 and VLA-4 was analysed in PB and PC samples. We found that T. canis infection induced systemic eosinophilia from post-infection day 3, peaking on days 6, 12 and 24 in PB, PC and BALF samples respectively. Eosinophilia was more pronounced in PB and PC samples than in BALF samples, and MK886 downregulated eosinophilia to varying degrees in the different sample types. In PB and PC samples, T. canis infection caused early upregulation of Mac-1 with late changes in the VLA-4 profile, whereas MK886 had opposite effects. The distinct time-dependent eosinophilia peaks and differential involvement of leukotrienes in integrin expression demonstrate that, despite the systemic eosinophilia triggered by T. canis infection, inflammatory responses vary by compartment.
Anibal
F F
FF
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil.
Rogerio
A P
AP
Malheiro
A
A
Machado
E R
ER
Martins-Filho
O A
OA
Andrade
M C
MC
Soares
E G
EG
Medeiros
A I
AI
Faccioli
L H
LH
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D004802:Eosinophilia / Q000188:drug therapy* / Q000276:immunology; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D007211:Indoles / Q000627:therapeutic use*; D039041:Integrin alpha4beta1 / Q000096:biosynthesis / Q000187:drug effects; D016859:Lipoxygenase Inhibitors / Q000627:therapeutic use*; D016177:Macrophage-1 Antigen / Q000096:biosynthesis / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D014120:Toxocariasis / Q000188:drug therapy* / Q000276:immunology; D002722:Chlorobenzenes
D007211:Indoles; D039041:Integrin alpha4beta1; D016859:Lipoxygenase Inhibitors; D016177:Macrophage-1 Antigen; C060893:MK-886; D002722:Chlorobenzenes