title: Decreased plasma cytokines are associated with low platelet counts in aplastic anemia and immune thrombocytopenic purpura.
abstract: BACKGROUND
  We previously found plasma levels of CD40 ligand (CD40L), chemokine (C-X-C motif) ligand 5 (CXCL5), chemokine (C-C motif) ligand 5 (CCL5) and epidermal growth factor (EGF) to be low in aplastic anemia (AA) patients and to be correlated with platelet count.
  
  
  OBJECTIVE
  To study the association of CD40L, CXCL5, CCL5 and EGF with platelets.
  
  
  METHODS
  We measured cytokines in the plasma of immune thrombocytopenic purpura (ITP) and AA patients using the Luminex assay and confirmed the results in a mouse model and in vitro experiments.
  
  
  RESULTS
  Both ITP and AA showed similarly low levels of CD40L, CXCL5, CCL5 and EGF, compared with healthy controls. In ITP, levels of these proteins were significantly greater in patients with higher platelet counts than in those with lower platelet counts. In a murine thrombocytopenia model, levels of CD40L, CXCL5, CCL5 and EGF decreased with platelet count after immune-mediated destruction, while the cytokine levels increased when the platelet count recovered. In vitro, concentrations of these cytokines in the supernatants of platelet suspensions were proportional to platelet numbers, and levels in sera prepared by simple blood coagulation were equivalent to those in platelet-rich plasma-converted sera. mRNA expression for CXCL5, CCL5 and EGF was higher in platelets than in megakaryocytes, peripheral blood mononuclear cells, granulocytes and non-megakaryocytic bone marrow cells.
  
  
  CONCLUSIONS
  Plasma CD40L, CXCL5, CCL5 and EGF are mainly platelet-derived, suggesting a role of platelets in immune responses and inflammation. Measurement of CD40L, CXCL5, CCL5 and EGF in human blood allowed testable inferences concerning physiology and pathophysiology in quantitative platelet disorders.
authors.affiliation: Hematology Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. fengx2@nhlbi.nih.gov
authors.forename: X
authors.initials: X
authors.lastname: Feng
authors.forename: P
authors.initials: P
authors.lastname: Scheinberg
authors.forename: L
authors.initials: L
authors.lastname: Samsel
authors.forename: O
authors.initials: O
authors.lastname: Rios
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.forename: J P
authors.initials: JP
authors.lastname: McCoy
authors.forename: W
authors.initials: W
authors.lastname: Ghanima
authors.forename: J B
authors.initials: JB
authors.lastname: Bussel
authors.forename: N S
authors.initials: NS
authors.lastname: Young
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000741:Anemia, Aplastic / Q000097:blood* / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000276:immunology* / Q000378:metabolism; D023201:CD40 Ligand / Q000097:blood; D016022:Case-Control Studies; D018946:Chemokine CCL5 / Q000097:blood; D054365:Chemokine CXCL5 / Q000097:blood; D002648:Child; D016207:Cytokines / Q000097:blood* / Q000235:genetics; D004195:Disease Models, Animal; D015536:Down-Regulation; D004815:Epidermal Growth Factor / Q000097:blood; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D010976:Platelet Count; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood* / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000097:blood; D055815:Young Adult
chemical_list: D015415:Biomarkers; C483024:CCL5 protein, human; C486263:CXCL5 protein, human; D018946:Chemokine CCL5; D054365:Chemokine CXCL5; D016207:Cytokines; D018836:Inflammation Mediators; D012333:RNA, Messenger; D023201:CD40 Ligand; D004815:Epidermal Growth Factor