dc.contributor.author | Ochiel, DO | |
dc.contributor.author | Awandare, GA | |
dc.contributor.author | Keller, CC | |
dc.contributor.author | Hittner, JB | |
dc.contributor.author | Kremsner, PG | |
dc.contributor.author | Weinberg, JB | |
dc.contributor.author | Perkins, DJ | |
dc.date.accessioned | 2013-06-12T15:18:52Z | |
dc.date.available | 2013-06-12T15:18:52Z | |
dc.date.issued | 2005-07 | |
dc.identifier.citation | Infect Immun. 2005 Jul;73(7):4190-7. | en |
dc.identifier.uri | http://hinari-gw.who.int/whalecomwww.ncbi.nlm.nih.gov/whalecom0/pubmed/15972509 | |
dc.identifier.uri | http://erepository.uonbi.ac.ke:8080/xmlui/handle/123456789/32519 | |
dc.description.abstract | Chemokines regulate the host immune response to a variety of infectious pathogens. Since the role of chemokines in regulating host immunity in children with Plasmodium falciparum malaria has not previously been reported, circulating levels of beta-chemokines (MIP-1alpha, MIP-1beta, and RANTES) and their respective transcriptional profiles in ex vivo peripheral blood mononuclear cells (PBMCs) were investigated. Peripheral blood MIP-1alpha and MIP-1beta levels were significantly elevated in mild and severe malaria, while RANTES levels decreased with increasing disease severity. Beta-chemokine gene expression profiles in blood mononuclear cells closely matched those of circulating beta-chemokines, illustrating that PBMCs are a primary source for the observed pattern of beta-chemokine production during acute malaria. Statistical modeling revealed that none of the chemokines was significantly associated with either parasitemia or anemia. Additional investigations in healthy children with a known history of malaria showed that children with prior severe malaria had significantly lower baseline RANTES production than children with a history of mild malaria, suggesting inherent differences in the ability to produce RANTES in these two groups. Baseline MIP-1alpha and MIP-1beta did not significantly differ between children with prior severe malaria and those with mild malaria. Additional in vitro experiments in PBMCs from healthy, malaria-naïve donors revealed that P. falciparum-derived hemozoin (Hz; malarial pigment) and synthetic Hz (beta-hematin) promote a similar pattern of beta-chemokine gene expression. Taken together, the results presented here demonstrate that children with severe malaria have a distinct profile of beta-chemokines characterized by increased circulating levels of MIP-1alpha and MIP-1beta and decreased RANTES. Altered patterns of circulating beta-chemokines result, at least in part, from Hz-induced changes in beta-chemokine gene expression in blood mononuclear cells. | en |
dc.language.iso | en | en |
dc.publisher | University of Nairobi. | en |
dc.title | Differential regulation of beta-chemokines in children with Plasmodium falciparum malaria | en |
dc.type | Article | en |
local.publisher | Reproductive Biology Unit, Department of Animal Physiology, University of Nairobi, Kenya | en |