Article

Platelet factor 4 mediates inflammation in experimental cerebral malaria.

Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, MD 21205, USA.
Cell host & microbe (Impact Factor: 13.02). 09/2008; 4(2):179-87. DOI: 10.1016/j.chom.2008.07.003
Source: PubMed

ABSTRACT Cerebral malaria (CM) is a major complication of Plasmodium falciparum infection in children. The pathogenesis of CM involves vascular inflammation, immune stimulation, and obstruction of cerebral capillaries. Platelets have a prominent role in both immune responses and vascular obstruction. We now demonstrate that the platelet-derived chemokine, platelet factor 4 (PF4)/CXCL4, promotes the development of experimental cerebral malaria (ECM). Plasmodium-infected red blood cells (RBCs) activated platelets independently of vascular effects, resulting in increased plasma PF4. PF4 or chemokine receptor CXCR3 null mice had less severe ECM, including decreased T cell recruitment to the brain, and platelet depletion or aspirin treatment reduced the development of ECM. We conclude that Plasmodium-infected RBCs can directly activate platelets, and platelet-derived PF4 then contributes to immune activation and T cell trafficking as part of the pathogenesis of ECM.

0 Bookmarks
 · 
128 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Despite their small size and anucleate status, platelets have diverse roles in vascular biology. Not only are platelets the cellular mediator of thrombosis but platelets are also immune cells that initiate and accelerate many vascular inflammatory conditions. Platelets are linked to the pathogenesis of inflammatory diseases such as atherosclerosis, malaria infection, transplant rejection, and rheumatoid arthritis. In some contexts platelet immune functions are protective, while in others platelets contribute to adverse inflammatory outcomes. In this review we will discuss platelet and platelet derived mediator interactions with the innate and acquired arms of the immune system and platelet-vessel wall interactions that drive inflammatory disease. There have been many recent publications indicating both important protective and adverse roles for platelets in infectious disease. Because of this new accumulating data, and the fact that infectious disease continues to be a leading cause of death globally, we will also focus on new and emerging concepts related to platelet immune and inflammatory functions in the context of infectious disease.
    Blood 02/2014; · 9.78 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The ghrelin axis is involved in the regulation of metabolism, energy balance, and the immune, cardiovascular and reproductive systems. The manipulation of this axis has potential for improving economically valuable traits in production animals, and polymorphisms in the ghrelin (GHRL) and ghrelin receptor (GHSR) genes have been associated with growth and carcass traits. Here we investigate the structure and expression of the ghrelin gene (GHRL) in sheep, Ovis aries.
    BMC Veterinary Research 09/2014; 10:211. · 1.74 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Platelet factor 4 (PF4) was the first discovered CXC chemokine and is found in platelet granules at very high concentration. Now, it is becoming increasingly evident that PF4 actively participates in inflammation and immune response. Recent paper demonstrated that PF4 limits the development and response of the Th17 cells and assisted in regulatory T cell development in transplantation. But, the immunoregulatory role of PF4 in tumor has little known and needs to be further investigated. In our current study, wild-type mice are inoculated with melanoma cell line B16-F10 (1 × 10(6)/mouse) and treated with PF4. PF4 inhibits B16 tumor growth and decreases γδ cell infiltration. The expression of interleukin (IL)-17, IL-6, and p-signal transducer and activator of transcription-3 (Stat3) was markedly decreased with treatment of PF4 compared with control in vivo and in vitro. And, the suppressed tumor growth induced by PF4 is abolished by additional treatment of recombinant mouse IL (rmIL)-17. PF4 also induces suppressor of cytokine signaling 3 (SOCS3) upregulations, and PF4 fails to suppress expression of p-Stat3, IL-17, and IL-6 in cells transfected with SOCS3 short interfering RNA (siRNA). In conclusion, PF4 inhibits IL-17/Stat3 pathway via upregulation of SOCS3 expression and may contribute to suppressing tumor growth in murine models of melanoma.
    Inflammation 05/2014; · 1.92 Impact Factor

Full-text (2 Sources)

Download
41 Downloads
Available from
May 19, 2014