Stromal cell derived factor 1 synthesis by spleen cells in rodent malaria, and the effects of in vivo supplementation of SDF-1α and CXCR4 receptor blocker

The mechanisms of malaria parasite clearance in the host are not well understood, but are ascribed to the intact spleen the site for parasite clearance. The infection induces a huge increase in spleen volume and cellularity. There is, however, a lack of studies on the splenic production of chemokines, which are small proteins that control homing and activation of immune cells and must be crucial for organized tissue growth. We studied the spleen cell production of SDF-1 a primordial chemokine of the CXCL12 class, through mRNA Reverse transcriptase and polymerase chain reaction of both isoforms, alpha and beta, in lethal (Plasmodium berghei ANKA) and non-lethal recrudescent malaria (Plasmodium chabaudi CR) in BALB/c and C57BL/6 mouse strains. In non-lethal P. chabaudi malaria in C57BL/6 mice, SDF-1alpha. mRNA production clearly peaked before the control of parasitemia, a fact not observed in the same mouse strain infected with lethal P. berghei, when this production was lower and without peaks. The infection of BALB/c mice infected with the same Plasmodium species led to a similar evolution of parasitemia and also chemokine production, albeit at lower levels. SDF-1beta synthesis was more constant and regular during both infections, presenting some variation but usually occurring at all the experimental times. Supplementation of lethal models with SDF-1alpha i.p., at the time when endogenous stromal cell chemokine production peaked in non-lethal models. induced a clear reduction in parasitemia, probably with prolonged host survival. Blocking SDF-1 action by administration of T-140, a CXCR4 receptor blocker, caused an increase in circulating parasites in the usually benign non-lethal P. chabaudi malaria in C57BL/6 mice, mainly at recrudescence of parasitemia. These data suggest that SDF-1alpha production in the spleen plays an important role in rodent malaria, and its supplementation was found to partially correct defects in the control of malaria in lethal models. (C) 2002 Elsevier Science B.V. All rights reserved.