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John D. Loike, Ph.D. Co-Director of Graduate Studies Department Physiology & Cellular Biophysics E-mail: jdl5@columbia.edu Tel: (212) 305-1510 Office: BB 11-1111 Fax: (212) 305-5775 http://www.columbia.edu/~jdl5/ |
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CURRENT RESEARCH THE REGULATION OF LEUKOCYTE RESPONSES TO INFLAMMATION. My current research interest focuses on the regulation of leukocyte chemotaxis through physiological and pathological matrices. I have found that the composition of the extracellular matrix affects chemotactic properties of both neutrophils and monocytes. Neutrophils rapidly migrate across physiological matrices such as collagen or basement membrane proteins in response to the major classes of chemoattractants such as fMLP, TNF, IL-8, C5a, or LTB4. In contrast, the capacity of neutrophils to migrate across a fibrin gel depends on the nature of the chemoattractant. Only IL-8 and LTB4 promote chemotaxis across such filters. No neutrophil migration across fibrin gels is observed in response to fMLP, TNF, or C5a. Equally important is the fact that fMLP blocks chemotaxis across fibrin when other chemokines (IL-8 or LTB4) are present. These studies suggest that chemoattractants serves different functions depending upon the nature of the matrix protein. Integrins play a major role in regulating chemotaxis. I have found that certain chemokines, such as fMLP, promote beta 1 integin activation and inhibit chemotaxis whereas chemokines that promote chemotaxis activate beta 2 integrins. Fibrin is not the only pathological matrix that regulates selective chemotaxis. Tenascin, an extracellular matrix protein found in tumor stroma and atherosclerotic lesions also inhibits both monocyte and neutrophil chemotaxis. Beta amyloid fibrils which are involved in the pathology of Alzheimer's disease also block leukocyte and microglial cell chemotaxis. These systems will be used to elucidate the signal transduction pathways that regulate these processes. SELECTED PUBLICATIONS Li, Y., Karlin, A., Loike, J.D., and Silverstein, S.C. 2004. Determination of the critical concentration of neutrophils required to block bacterial growth in tissues. J Exp Med. 200(5):613-22. Loike, J.D., Shabtai, D.Y., Neuhut, R., Malitzky, S., Lu, E., Husemann, J., Goldberg, I.J., and Silverstein, S.C. 2004. Statin inhibition of Fc receptor-mediated phagocytosis by macrophages is modulated by cell activation and cholesterol. Arterioscler Thromb Vasc Biol. Nov;24(11):2051-6. Wyss-Coray, T., Loike, J.D., Brionne, T.C., Lu, E., Anankov, R., Yan, F., Silverstein, S.C., and Husemann, J. 2003. Adult mouse astrocytes degrade amyloid-beta in vitro and in situ. Nat Med. Apr;9(4):453-7 Loike, J.D., and Tendler, M.D. 2003. Ma adam va-teda-ehu: halakhic criteria for defining human beings. Tradition. Summer;37(2):1-19. Husemann, J., Loike, J.D., Anankov, R., Febbraio, M., and Silverstein, S.C. 2002. Scavenger receptors in neurobiology and neuropathology: their role on microglia and other cells of the nervous system. Glia. 2002 Nov;40(2):195-205. Loike, J.D., and Tendler, M.D. 2002. Revisiting the definition of homo sapiens. Kennedy Inst Ethics J. Dec;12(4):343-50. Li, Y., Karlin, A., Loike, J.D., and Silverstein, S.C. 2002. A critical concentration of neutrophils is required for effective bacterial killing in suspension. Proc Natl Acad Sci U S A. Jun 11;99(12):8289-94. Berger, M., Budhu, S., Lu, E., Li, Y., Loike, D., Silverstein, S.C., and Loike, J.D. 2002. Different G(i)-coupled chemoattractant receptors signal qualitatively different functions in human neutrophils. J Leukoc Biol. May;71(5):798-806. |
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