The overall goal of the project is to elucidate the mechanisms that regulate the traffic of leukocytes in the body. Harmful leukocyte migration into the heart in myocardial infarction (reperfusion injury), into the joint tissue in rheumatoid arthritis and into the pancreas in diabetes are examples of diseases where leukocytes cause extensive destruction. Damages can be prevented by inhibiting leukocyte trafficking to those sites. Also metastasising malignant cells often use the same mechanisms as leukocytes when extravasating from the blood to different organs. The results obtained in this research can be utilized when new types of drugs are developed to treat harmful inflammations and cancer.

• Enzymatic and adhesive properties of vascular adhesion protein-1 (VAP-1)
• VAP-1 transgenic and knockout animals
• Targeting lymphocyte and endothelial cell functions during the development of diabetes
• Homing properties of tumor infiltrating lymphocytes
• Enzymatic and adhesive properties of CD73
• Identification of molecules involved in lymphocyte exit from the lymph nodes

• Stolen CM, Marttila-Ichihara F, Koskinen K, Yegutkin GG, Turja R, Bono P, Skurnik M, Hanninen A, Jalkanen S, Salmi M. Absence of the endothelial oxidase AOC3 leads to abnormal leukocyte traffic in vivo. Immunity 22:105-115, 2005.
PubMed - abstract
• Merinen M, Irjala H, Salmi M, Jaakkola I, Hänninen A, Jalkanen S. Vascular adhesion protein-1 is involved in both acute and chronic inflammation in the mouse. Am J Pathol 166:793-800, 2005.
PubMed - abstract
• Stolen CM, Yegutkin GG, Kurkijärvi R, Bono P, Alitalo K, Jalkanen S. Origins of serum semicarbazide-sensitive amine oxidase. Circ Res 95:50-57, 2004.
PubMed - abstract
• Martelius T, Salaspuro V, Salmi M, Krogerus L, Hockerstedt K, Jalkanen S, Lautenschlager I. Blockade of vascular adhesion protein-1 inhibits lymphocyte infiltration in rat liver allograft rejection. Am J Pathol 165:1993-2001, 2004.
PubMed - abstract
• Salmi M, Koskinen K, Henttinen T, Elima K, Jalkanen S. CLEVER-1 mediates lymphocyte transmigration through vascular and lymphatic endothelium. Blood 104:3849-3857, 2004.
PubMed - abstract
• Stolen CM, Madanat R, Kari S, Yegutkin GG, Sariola H, Jalkanen S. Semicarbazide sensitive amine oxidase overexpression mimics insulin's actions and produces diabetes-like complications. Faseb J 18:702-704, 2004.
PubMed - abstract
• Koskinen K, Vainio PJ, Smith DJ, Pihlavisto M, Ylä-Herttuala S, Jalkanen S, Salmi M. Granulocyte transmigration through endothelium is regulated by the oxidase activity of vascular adhesion protein-1 (VAP-1). Blood, Jan 15, (Epub ahead of print), 2004.
PubMed - abstract
• Niemelä J, HenttinenT, Yegutkin G, Airas L, Kujari A-M, Rajala P, Jalkanen S. Interferon-alpha induced adenosine production on the endothelium: a mechanism mediated by CD73 (ecto-5´-nucleotidase) upregulation. J Immunol 172:1646-1653, 2004.
PubMed - abstract
• Irjala H, Alanen K, Grenman R, Heikkila P, Joensuu H, Jalkanen S. Mannose receptor (MR) and common lymphatic endothelial and vascular endothelial receptor (CLEVER)-1 direct the binding of cancer cells to the lymph vessel endothelium. Cancer Res, 63:4671-6, 2003.
PubMed - abstract
• Jaakkola I, Jalkanen S, Hänninen A. Diabetogenic T cells are primed both in pancreatic and gut-associated lymph nodes in NOD mice. Eur J Immunol, 33:3255-3264, 2003.
PubMed - abstract
• Henttinen T, Jalkanen S, Yegutkin GG. Adherent leukocytes prevent adenosine formation and impair endothelial barrier function by Ecto-5'-nucleotidase/CD73-dependent mechanism. J Biol Chem, 278:24888-95. Epub Apr 21, 2003.
PubMed - abstract
• Yegutkin GG, Samburski SS, Jalkanen S. Soluble purine-converting enzymes circulate in human blood and regulate extracellular ATP level via counteracting pyrophosphatase and phosphotransfer reactions. FASEB J. 17:1328-30. Epub May 20, 2003.
PubMed - abstract
• Maksimow M, Santanen M, Jalkanen S, Hanninen A. Responding naive T cells differ in their sensitivity to Fas engagement: early death of many T cells is compensated by costimulation of surviving T cells. Blood, 101:4022-8. Epub Jan 16, 2003.
PubMed - abstract
• Maula SM, Luukkaa M, Grenman R, Jackson D, Jalkanen S, Ristamaki R. Intratumoral lymphatics are essential for the metastatic spread and prognosis in squamous cell carcinomas of the head and neck region. Cancer Res, 63(8):1920-6, 2003
PubMed - abstract
• Irjala H, Elima K, Johansson EL, Merinen M, Kontula K, Alanen K, Grenman R, Salmi M, Jalkanen S. The same endothelial receptor controls lymphocyte traffic both in vascular and lymphatic vessels. Eur J Immunol, 33:815-24, 2003.
PubMed - abstract
• Jaakkola I, Merinen M, Jalkanen S, Hanninen A. Ly6C induces clustering of LFA-1 (CD11a/CD18) and is involved in subtype-specific adhesion of CD8 T cells. J Immunol, 170:1283-90, 2003.
PubMed - abstract

Doctoral Theses

• Circulating form of vascular adhesion protein-1 (VAP-1). Riikka Kurkijärvi, 2004
• Adhesion molecules in the dissemination and the prognosis of cancer. Special reference to CD44, VAP-1 and LYVE-1. Sanna-Mari Maula, 2003
• Lymphocyte traffic and adhesion receptors in the pancreas and the gut: special emphasis on autoimmune diabetes. Ilkka Jaakkola, 2003
• An immunotherapeutic approach to cancer of the head and neck. Heikki Irjala, 2002
• Role of soluble mediators in leukocyte activation and adhesion to the endothelium: special emphasis on cytokine and purine mediated pathways. Tiina Henttinen, 2001
• Leukocyte adhesion to endothelium in vitro and in vivo: role of vascular adhesion protein-1 (VAP-1). Sami Tohka, 2001
• Vascular adhesion protein-1 as a target for anti-adhesive therapy and inflammation diagnostics. Kimmo Jaakkola, 2000
• The regulation of lymphocyte trafficking: role of the multifunctional adhesion molecules VAP-1 and CD73. Anna-Maija Kujari, 1998
• Lymphocyte-endothelial cell interactions: molecular analysis of vascular adhesion protein-1 (VAP-1). Petri Bono, 1998
• On the role of CD73 in lymphocyte adhesion. Laura Airas, 1996
• Mechanisms of lymphocyte accumulation in the endocrine pancreas in insulin-ependent diabetes. Arno Hänninen, 1995
• Tissue-selective lymphocyte-endothelial cell interactions in man. Marko Salmi, 1995
• Prognostic factors in non-Hodgkin's lymphoma: a special reference to CD44. Ristamäki, 1995