title: Platelet glycoprotein Ib-IX as a regulator of systemic inflammation.
abstract: OBJECTIVE
  The platelet glycoprotein Ib-IX (GP Ib-IX) receptor is a well-characterized adhesion receptor supporting hemostasis and thrombosis via interactions with von Willebrand factor. We examine the GP Ib-IX/von Willebrand factor axis in murine polymicrobial sepsis, as modeled by cecal ligation and puncture (CLP).
  
  
  RESULTS
  Genetic absence of the GP Ib-IX ligand, von Willebrand factor, prolongs survival after CLP, but absence of the receptor, GP Ib-IX, does not. Because absence of either von Willebrand factor or GP Ib-IX significantly impairs hemostasis and thrombosis, we sought to define additional GP Ib-IX-dependent pathways impacting survival in the CLP model. We document that the absence of GP Ib-IX leads to reduced platelet-neutrophil and platelet-monocyte interactions. Twenty-four hours after CLP, absence of GP Ib-IX coincides with an alteration in cytokine levels, such as tumor necrosis factor-α secreted by monocytes, and increased macrophage-1 antigen expression by neutrophils.
  
  
  CONCLUSIONS
  In contrast to the well-characterized proinflammatory properties of platelets, we describe in the CLP model an anti-inflammatory property associated with platelet GP Ib-IX. Thus, a single platelet receptor displays a dual modulatory role in both the thrombotic and inflammatory pathways associated with polymicrobial sepsis. In sharing leucine-rich motifs with toll-like receptors, platelet GP Ib-IX can be considered a multifunctional participant in hemostasis, thrombosis, and the inflammatory cascade. The results highlight a dynamic role for platelets in systemic inflammation and add to the complex pathophysiologic events that occur during the dysregulated coagulation and inflammation associated with sepsis.
authors: From the Departments of Physiology and Biophysics (A.C., S.R., J.D., J.W.) and Pathology (S.R.P.), University of Arkansas for Medical Sciences, Little Rock.
authors: Adam
authors: A
authors: Corken
authors: Susan
authors: S
authors: Russell
authors: Judith
authors: J
authors: Dent
authors: Steven R
authors: SR
authors: Post
authors: Jerry
authors: J
authors: Ware
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000276:immunology / Q000378:metabolism*; D002432:Cecum / Q000382:microbiology / Q000601:surgery; D002450:Cell Communication; D004195:Disease Models, Animal; D006487:Hemostasis; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D008024:Ligands; D008026:Ligation; D016177:Macrophage-1 Antigen / Q000097:blood; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000235:genetics / Q000378:metabolism*; D018805:Sepsis / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D015398:Signal Transduction; D013927:Thrombosis / Q000097:blood / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014841:von Willebrand Factor / Q000235:genetics / Q000378:metabolism
chemical_list: C508598:IL4 protein, human; D008024:Ligands; D016177:Macrophage-1 Antigen; D019038:Platelet Glycoprotein GPIb-IX Complex; D014409:Tumor Necrosis Factor-alpha; C094990:adhesion receptor; D014841:von Willebrand Factor; D015847:Interleukin-4
keywords: cytokines; monocytes; neutrophils; platelet glycoprotein GPIb-IX complex; sepsis