Potential role of the chemokine macrophage inflammatory protein 1alpha in human and experimental schistosomiasis.
In human schistosomiasis, the concentrations of the chemokine macrophage inflammatory protein 1alpha (MIP-1alpha/CCL3) is greater in the plasma of patients with clinical hepatosplenic disease. The objective of the present study was to confirm the ability of CCL3 to detect severe disease in patients classified by ultrasonography (US) and to evaluate the potential role of CCL3 in Schistosoma mansoni-infected mice. CCL3 was measured by enzyme-linked immunosorbent assay in the plasma of S. mansoni-infected patients. CCL3-deficient mice were infected with 25 cercariae, and various inflammatory and infectious indices were evaluated. The concentration of CCL3 was higher in the plasma of S. mansoni-infected than noninfected patients. Moreover, CCL3 was greater in those with US-defined hepatosplenic than with the intestinal form of the disease. In CCL3-deficient mice, the size of the granuloma and the liver eosinophil peroxidase activity and collagen content were diminished compared to wild-type mice. In CCL3-deficient mice, the worm burden after 14 weeks of infection, but not after 9 weeks, was consistently smaller. The in vitro response of mesenteric lymph node cells to antigen stimulation was characterized by lower levels of interleukin-4 (IL-4) and IL-10. CCL3 is a marker of disease severity in infected humans, and experimental studies in mice suggest that CCL3 may be a causative factor in the development of severe schistosomiasis.
Souza
Adriano L S
AL
Laboratório de Imunofarmacologia, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Roffê
Ester
E
Pinho
Vanessa
V
Souza
Danielle G
DG
Silva
Adriana F
AF
Russo
Remo C
RC
Guabiraba
Rodrigo
R
Pereira
Cíntia A J
CA
Carvalho
Flávia M
FM
Barsante
Michele M
MM
Correa-Oliveira
Rodrigo
R
Fraga
Lúcia A O
LA
Negrão-Correa
Deborah
D
Teixeira
Mauro M
MM
D000818:Animals; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D002908:Chronic Disease; D003094:Collagen / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D047209:Eosinophil Peroxidase / Q000378:metabolism; D005260:Female; D006801:Humans; D007422:Intestines / Q000473:pathology; D008099:Liver / Q000473:pathology; D019402:Macrophage Inflammatory Proteins / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012555:Schistosomiasis mansoni / Q000209:etiology* / Q000276:immunology / Q000473:pathology
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D016207:Cytokines; D019402:Macrophage Inflammatory Proteins; D003094:Collagen; D047209:Eosinophil Peroxidase