PMID- 20454664 OWN - NLM STAT- MEDLINE DCOM- 20100907 LR - 20211203 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 5 IP - 5 DP - 2010 May 3 TI - Platelet factor 4 regulation of monocyte KLF4 in experimental cerebral malaria. PG - e10413 LID - 10.1371/journal.pone.0010413 [doi] LID - e10413 AB - 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. FAU - Srivastava, Kalyan AU - Srivastava K AD - Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, New York, United States of America. FAU - Field, David J AU - Field DJ FAU - Aggrey, Angela AU - Aggrey A FAU - Yamakuchi, Munekazu AU - Yamakuchi M FAU - Morrell, Craig N AU - Morrell CN LA - eng GR - R01 HL093179/HL/NHLBI NIH HHS/United States GR - R01 HL094547/HL/NHLBI NIH HHS/United States GR - R01HL093179/HL/NHLBI NIH HHS/United States GR - R01HL094547/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20100503 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Cytokines) RN - 0 (KLF4 protein, human) RN - 0 (Klf4 protein, mouse) RN - 0 (Kruppel-Like Factor 4) RN - 0 (Kruppel-Like Transcription Factors) RN - 37270-94-3 (Platelet Factor 4) SB - IM MH - Animals MH - Cytokines/biosynthesis MH - Humans MH - Kruppel-Like Factor 4 MH - Kruppel-Like Transcription Factors/*metabolism MH - Malaria, Cerebral/*metabolism/*pathology MH - Mice MH - Mice, Inbred C57BL MH - Monocytes/*metabolism MH - Platelet Factor 4/*metabolism PMC - PMC2862712 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2010/05/11 06:00 MHDA- 2010/09/08 06:00 PMCR- 2010/05/03 CRDT- 2010/05/11 06:00 PHST- 2009/12/17 00:00 [received] PHST- 2010/04/08 00:00 [accepted] PHST- 2010/05/11 06:00 [entrez] PHST- 2010/05/11 06:00 [pubmed] PHST- 2010/09/08 06:00 [medline] PHST- 2010/05/03 00:00 [pmc-release] AID - 09-PONE-RA-14991R1 [pii] AID - 10.1371/journal.pone.0010413 [doi] PST - epublish SO - PLoS One. 2010 May 3;5(5):e10413. doi: 10.1371/journal.pone.0010413.