Abstract

PP14 is an anti-inflammatory cytokine secreted by cells of the reproductive tract. Dr. Tykocinski has cloned a unique molecular form of PP14 produced in megakaryocytes and platelets and has developed both prokaryotic and eukaryotic expression systems for PP14. He proposes (1) molecular studies of human hematopoietic PP14 and its hydrophobic ligands and receptors; (2) further characterization of human hematopoietic PP14 and its immunosuppressive functions in in vitro systems; (3) studies of hematopoietic PP14 in platelets and its potential immunopathological consequences; (4) assessment of in vivo functions of PP14 in animal model systems, after prior cloning of respective animal PP14 homologues. Two central hypotheses will be tested: (1) PP14 and, in particular, human hematopoietic PP14 has immunotherapeutic potential as an anti-inflammatory cytokine for the treatment of inflammatory disorders; (2) PP14 from platelets is immunopathogenic in certain clinical settings.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI038960-05
Application #
6149803
Study Section
Special Emphasis Panel (ZRG3-MEP (01))
Program Officer
Quill, Helen R
Project Start
1996-02-15
Project End
2001-01-31
Budget Start
2000-02-01
Budget End
2001-01-31
Support Year
5
Fiscal Year
2000
Total Cost
$341,332
Indirect Cost

  Institution

Name
University of Pennsylvania
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

Ish-Shalom, Eliran; Gargir, Ari; Andre, Sabine et al. (2006) alpha2,6-Sialylation promotes binding of placental protein 14 via its Ca2+-dependent lectin activity: insights into differential effects on CD45RO and CD45RA T cells. Glycobiology 16:173-83
Mishan-Eisenberg, Galit; Borovsky, Zipora; Weber, Matthew C et al. (2004) Differential regulation of Th1/Th2 cytokine responses by placental protein 14. J Immunol 173:5524-30
Rachmilewitz, Jacob; Borovsky, Zipora; Riely, Gregory J et al. (2003) Negative regulation of T cell activation by placental protein 14 is mediated by the tyrosine phosphatase receptor CD45. J Biol Chem 278:14059-65
Tykocinski, Mark L; Chen, Aoshuang; Huang, Jui-Han et al. (2003) New designs for cancer vaccine and artificial veto cells: an emerging palette of protein paints. Immunol Res 27:565-74
Rachmilewitz, Jacob; Borovsky, Zipora; Mishan-Eisenberg, Galit et al. (2002) Focal localization of placental protein 14 toward sites of TCR engagement. J Immunol 168:2745-50
Moody, D Branch; Briken, Volker; Cheng, Tan-Yun et al. (2002) Lipid length controls antigen entry into endosomal and nonendosomal pathways for CD1b presentation. Nat Immunol 3:435-42
Rachmilewitz, J; Riely, G J; Huang, J H et al. (2001) A rheostatic mechanism for T-cell inhibition based on elevation of activation thresholds. Blood 98:3727-32
Riely, G J; Rachmilewitz, J; Koo, P H et al. (2000) alpha2-macroglobulin modulates the immunoregulatory function of the lipocalin placental protein 14. Biochem J 351 Pt 2:503-8
Rachmilewitz, J; Riely, G J; Tykocinski, M L (1999) Placental protein 14 functions as a direct T-cell inhibitor. Cell Immunol 191:26-33
Miller, R E; Fayen, J D; Chakraborty, S et al. (1998) A receptor for the lipocalin placental protein 14 on human monocytes. FEBS Lett 436:455-60

Showing the most recent 10 out of 12 publications