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.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Special Emphasis Panel (ZRG3-MEP (01))
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Quill, Helen R
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University of Pennsylvania
Schools of Medicine
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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
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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
Rachmilewitz, J; Tykocinski, M L (1998) Differential effects of chondroitin sulfates A and B on monocyte and B-cell activation: evidence for B-cell activation via a CD44-dependent pathway. Blood 92:223-9

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