Stromal cell-derived factor-1 production by spleen cells is affected by nitric oxide in protective immunity against blood-stage Plasmodium chabaudi CR in C57BL/6j mice.
Malaria, a major endemic tropical disease, is caused by the infection of blood cells by Plasmodium protozoa. Most patients control their parasitemia by a not fully understood spleen-dependent mechanism. SDF-1alpha is a chemokine produced by stromal cells such as reticular spleen cells. Nitric oxide (NO) has several immune functions, including killing of intracellular pathogens and its function in malaria is debated. We have previously shown that SDF-1alpha production peaks during the ascending parasitemia in Plasmodium chabaudi infection and its supplementation in lethal models could reduce the parasitemia. In the present study, we analyzed SDF-1 production by spleen cells as related to NO metabolism in the P. chabaudi rodent malaria model using IFN-gamma; TNFR and iNOS-knockout mice or iNOS-blocked, L-NAME- or aminoguanidine-treated mice. Parasitemia and production of SDF-1alpha and SDF-1beta were determined by RT-PCR. In vitro NO production by spleen adherent cells was also tested. The data showed that parasitemia was less intense in both iNOS(-/-) or NO-inhibited mice than in controls, with increased and long-lasting production of SDF-1alpha mRNA. In the absence of cytokines involved in the final regulation of NO production by effector cells, as is the case for TNFR(-/-) and GKO mice, the infection progressed in an uncontrolled manner regardless of SDF-1alpha production, suggesting that these cytokines must be involved in the control of parasitemia after the SDF-1alpha dependent process. The SDF-1beta isoform was constitutive in all experiments, with elevated levels only clearly seen in TNFR(-/-) mice. We conclude that SDF-1 is involved in the promotion of parasitemia control in malaria, and excessive NO could affect its production.
Garnica
Margoth Ramos
MR
Lab. Protozoologia, lnstituto de Medicina Tropical de São Paulo, Universidade de São Paulo, Av. Dr.E.C. Aguiar 470, 05403-000, SP, São Paulo, Brazil.
Silva
João Santana
JS
de Andrade Junior
Heitor Franco
HF
D000818:Animals; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D008288:Malaria / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016788:Plasmodium chabaudi / Q000187:drug effects / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D016207:Cytokines; D012333:RNA, Messenger; D009569:Nitric Oxide