title: Heparin binding protein (CAP37) differentially modulates endotoxin-induced cytokine production.
abstract: OBJECTIVE
  CAP37, also known as heparin-binding protein (HBP), is neutrophil-derived protein with multifunctional properties that include monocyte chemotaxis and the enhancement of LPS-induced tumor necrosis factor (TNF-alpha), IL-1, IL-6, and PGE2production from isolated monocytes, which suggest a generalized effect on LPS-induced monocyte activation. In this study, we tested whether HBP amplifies the release of other LPS-responsive cytokines from isolated human monocytes.
  
  
  METHODS
  Freshly isolated monocytes from 5 healthy donors were stimulated for 24 h with saline, LPS (10 ng/ml), HBP (10 microg/ml), or a combination of LPS + HBP. Cytokine levels in the supernate were measured with ELISA. ANOVA and Fisher's posthoc test were used to determine significance (p < 0.05). Differential display was used to assess cellular mRNA levels.
  
  
  RESULTS
  HBP alone induced the production of IL-8, macrophage inhibitory protein MIP-1alpha, and TNF-alpha. HBP increased the LPS-induced production of IL-8, MIP-1alpha, TNF-alpha, IL-1beta, but HBP did not increase the significant LPS-induced release of IL-10, monocyte chemoattractant protein MCP-1, and IL- 12. Differential display demonstrated that HBP induced an mRNA pattern that was different from the mRNA pattern induced by saline, LPS, or HBP + LPS, indicating multiple and different gene activation.
  
  
  CONCLUSIONS
  We conclude that HBP is not a general amplificator of LPS-induced monocyte activation but rather a molecule that targets the production of a distinct set of mediators including pro-inflammatory cytokines such as TNF-alpha and IL-1beta, but not the anti-inflammatory cytokine IL-10, nor IL-12 and MCP-1. The exact intracellular signaling pathways remain unknown but include mechanisms that alter gene transcription.
authors.affiliation: The Price Institute of Surgical Research, Department of Surgery, University of Louisville School of Medicine, Louisville, Kentucky 40292, USA. mheinzelmann@bluewin.ch
authors.forename: M
authors.initials: M
authors.lastname: Heinzelmann
authors.forename: E
authors.initials: E
authors.lastname: Kim
authors.forename: A
authors.initials: A
authors.lastname: Hofmeister
authors.forename: L E
authors.initials: LE
authors.lastname: Gordon
authors.forename: A
authors.initials: A
authors.lastname: Platz
authors.forename: W G
authors.initials: WG
authors.lastname: Cheadle
mesh_terms: D000704:Analysis of Variance; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins / Q000494:pharmacology*; D002352:Carrier Proteins / Q000494:pharmacology*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D016207:Cytokines / Q000096:biosynthesis* / Q000187:drug effects*; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology*; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011336:Probability; D012333:RNA, Messenger / Q000032:analysis; D012016:Reference Values; D012680:Sensitivity and Specificity; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000187:drug effects
chemical_list: C062991:AZU1 protein, human; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D002352:Carrier Proteins; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D016207:Cytokines; D007375:Interleukin-1; D016209:Interleukin-8; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha