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Publication : Platelet factor 4 regulation of monocyte KLF4 in experimental cerebral malaria.

First Author  Srivastava K Year  2010
Journal  PLoS One Volume  5
Issue  5 Pages  e10413
PubMed ID  20454664 Mgi Jnum  J:160842
Mgi Id  MGI:4455246 Doi  10.1371/journal.pone.0010413
Citation  Srivastava K, et al. (2010) Platelet factor 4 regulation of monocyte KLF4 in experimental cerebral malaria. PLoS One 5(5):e10413
abstractText  Cerebral malaria continues to be a difficult to treat complication of Plasmodium falciparum infection in children. We have shown that platelets can have major deleterious immune functions in experimental cerebral malaria (ECM). One of the platelet derived mediators we have identified as particularly important is platelet factor 4/CXCL4. Our prior work demonstrated that PF4(-/-) mice are protected from ECM, have reduced plasma cytokines, and have reduced T-cell trafficking to the brain. We now show that PF4 drives monocyte cytokine production in a Kruppel like factor 4 (KLF4) dependent manner. Monocyte depleted Plasmodium berghei infected mice have improved survival, and KLF4 is greatly increased in control, but not monocyte depleted mice. PF4(-/-) mice have less cerebral monocyte trafficking and no change in KLF4 expression. These data indicate that PF4 induction of monocyte KLF4 expression may be an important step in the pathogenesis of ECM.
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