HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Marazzi, S. Articles by Rüegg, C. Search for Related Content PubMed PubMed Citation Articles by Marazzi, S. Articles by Rüegg, C.

Characterization of Human Fibroleukin, a Fibrinogen-Like Protein Secreted by T Lymphocytes¹

Susanna Marazzi, Stephanie Blum^*, Reto Hartmann^*, Doris Gundersen^*, Magali Schreyer, Scott Argraves, Vladimir von Fliedner, Robert Pytela^§ and Curzio Rüegg^2,*

^* Centre Pluridisciplinaire d’Oncologie, School of Medicine, University of Lausanne, Lausanne, Switzerland; Ludwig Institute for Cancer Research, Lausanne Branch, Epalinges, Switzerland; Department of Cell Biology, Medical University of South Carolina, Charleston, SC 29425; and ^§ Lung Biology Center, Department of Medicine, University of California, San Francisco, CA 94143

We have recently cloned the human homologue of the murine pT49 cDNA (hpT49h), a transcript encoding a protein homologous to the ß- and -chains of fibrinogen. Here, we report the identification of the hpT49h gene product using mAbs generated against a peptide corresponding to the carboxyl-terminal end of the deduced protein and a recombinant protein fragment expressed in Escherichia coli. mAbs 23A6, 7B12, and 3F4 specifically recognized a protein of 70 kDa in reducing SDS-PAGE in the culture supernatant of 293T cells transiently transfected with the full length hpT49h cDNA and freshly isolated PBMC. Under nonreducing conditions, the material migrated with a molecular mass of 250 to 300 kDa, indicating that the 70-kDa protein forms a disulfide bonded complex. Because of its homology with fibrinogen, we have termed this protein fibroleukin. Fibroleukin is spontaneously secreted in vitro by freshly isolated CD4⁺ and CD8⁺ T lymphocytes. RT-PCR analysis revealed preferential expression of fibroleukin mRNA in memory T lymphocytes (CD3⁺/CD45R0⁺) compared with naive T lymphocytes (CD3⁺/CD45RA⁺). Fibroleukin production by PBMC was rapidly lost in culture. Production could be partially maintained in the presence of IFN-, while T lymphocyte activation had no effect. To demonstrate fibroleukin production in vivo, we analyzed colon mucosa by immunohistology. Fibroleukin staining was detected in the extracellular matrix of the T lymphocyte-rich upper portion of the lamina propria mucosa. While the exact function of fibroleukin remains to be defined, these data suggest that fibroleukin may play a role in physiologic lymphocyte functions at mucosal sites.

This article has been cited by other articles:

				M. Han, W. Yan, W. Guo, D. Xi, Y. Zhou, W. Li, S. Gao, M. Liu, G. Levy, X. Luo, et al. Hepatitis B Virus-induced hFGL2 Transcription Is Dependent on c-Ets-2 and MAPK Signal Pathway J. Biol. Chem., November 21, 2008; 283(47): 32715 - 32729. [Abstract] [Full Text] [PDF]

				M. Han, W. Yan, Y. Huang, H. Yao, Z. Wang, D. Xi, W. Li, Y. Zhou, J. Hou, X. Luo, et al. The Nucleocapsid Protein of SARS-CoV Induces Transcription of hfgl2 Prothrombinase Gene Dependent on C/EBP Alpha J. Biochem., July 1, 2008; 144(1): 51 - 62. [Abstract] [Full Text] [PDF]

				I. Shalev, H. Liu, C. Koscik, A. Bartczak, M. Javadi, K. M. Wong, A. Maknojia, W. He, M. F. Liu, J. Diao, et al. Targeted Deletion of fgl2 Leads to Impaired Regulatory T Cell Activity and Development of Autoimmune Glomerulonephritis J. Immunol., January 1, 2008; 180(1): 249 - 260. [Abstract] [Full Text] [PDF]

				J. Mu, D. Qu, A. Bartczak, M. J. Phillips, J. Manuel, W. He, C. Koscik, M. Mendicino, L. Zhang, D. A. Clark, et al. Fgl2 deficiency causes neonatal death and cardiac dysfunction during embryonic and postnatal development in mice Physiol Genomics, September 11, 2007; 31(1): 53 - 62. [Abstract] [Full Text] [PDF]

				D. Vu, C. Di Sanza, D. Caille, P. de Moerloose, H. Scheib, P. Meda, and M. Neerman-Arbez Quality control of fibrinogen secretion in the molecular pathogenesis of congenital afibrinogenemia Hum. Mol. Genet., November 1, 2005; 14(21): 3271 - 3280. [Abstract] [Full Text] [PDF]

				G. E. Olson, V. P. Winfrey, S. K. NagDas, and M. H. Melner Region-specific Expression and Secretion of the Fibrinogen-related Protein, fgl2, by Epithelial Cells of the Hamster Epididymis and Its Role in Disposal of Defective Spermatozoa J. Biol. Chem., December 3, 2004; 279(49): 51266 - 51274. [Abstract] [Full Text] [PDF]

				A. Ghanekar, M. Mendicino, H. Liu, W. He, M. Liu, R. Zhong, M. J. Phillips, G. A. Levy, and D. R. Grant Endothelial Induction of fgl2 Contributes to Thrombosis during Acute Vascular Xenograft Rejection J. Immunol., May 1, 2004; 172(9): 5693 - 5701. [Abstract] [Full Text] [PDF]

				W. W. Hancock, F. M. Szaba, K. N. Berggren, M. A. Parent, I. K. Mullarky, J. Pearl, A. M. Cooper, K. H. Ely, D. L. Woodland, I.-J. Kim, et al. Intact type 1 immunity and immune-associated coagulative responses in mice lacking IFN{gamma}-inducible fibrinogen-like protein 2 PNAS, March 2, 2004; 101(9): 3005 - 3010. [Abstract] [Full Text] [PDF]

				D. A. Clark, K. Foerster, L. Fung, W. He, L. Lee, M. Mendicino, U. R. Markert, R. M. Gorczynski, P. A. Marsden, and G. A. Levy The fgl2 prothrombinase/fibroleukin gene is required for lipopolysaccharide-triggered abortions and for normal mouse reproduction Mol. Hum. Reprod., February 1, 2004; 10(2): 99 - 108. [Abstract] [Full Text] [PDF]

				X. Zhao, K. E. Pearson, D. A. Stephan, and P. Russell Effects of Prostaglandin Analogues on Human Ciliary Muscle and Trabecular Meshwork Cells Invest. Ophthalmol. Vis. Sci., May 1, 2003; 44(5): 1945 - 1952. [Abstract] [Full Text] [PDF]

				C. W. Y. Chan, L. S. Kay, R. G. Khadaroo, M. W. C. Chan, S. Lakatoo, K. J. Young, L. Zhang, R. M. Gorczynski, M. Cattral, O. Rotstein, et al. Soluble Fibrinogen-Like Protein 2/Fibroleukin Exhibits Immunosuppressive Properties: Suppressing T Cell Proliferation and Inhibiting Maturation of Bone Marrow-Derived Dendritic Cells J. Immunol., April 15, 2003; 170(8): 4036 - 4044. [Abstract] [Full Text] [PDF]

				C. W. Y. Chan, M. W. C. Chan, M. Liu, L. Fung, E. H. Cole, J. L. Leibowitz, P. A. Marsden, D. A. Clark, and G. A. Levy Kinetic Analysis of a Unique Direct Prothrombinase, fgl2, and Identification of a Serine Residue Critical for the Prothrombinase Activity J. Immunol., May 15, 2002; 168(10): 5170 - 5177. [Abstract] [Full Text] [PDF]

				L. Hanlon, D. Argyle, D. Bain, L. Nicolson, S. Dunham, M. C. Golder, M. McDonald, C. McGillivray, O. Jarrett, J. C. Neil, et al. Feline Leukemia Virus DNA Vaccine Efficacy Is Enhanced by Coadministration with Interleukin-12 (IL-12) and IL-18 Expression Vectors J. Virol., September 15, 2001; 75(18): 8424 - 8433. [Abstract] [Full Text] [PDF]

				K. Liu, Y. Li, V. Prabhu, L. Young, K. G. Becker, P. J. Munson, and N.-p. Weng Augmentation in Expression of Activation-Induced Genes Differentiates Memory from Naive CD4+ T Cells and Is a Molecular Mechanism for Enhanced Cellular Response of Memory CD4+ T Cells J. Immunol., June 15, 2001; 166(12): 7335 - 7344. [Abstract] [Full Text] [PDF]

				G. A. Levy, M. Liu, J. Ding, S. Yuwaraj, J. Leibowitz, P. A. Marsden, Q. Ning, A. Kovalinka, and M. J. Phillips Molecular and Functional Analysis of the Human Prothrombinase Gene (HFGL2) and Its Role in Viral Hepatitis Am. J. Pathol., April 1, 2000; 156(4): 1217 - 1225. [Abstract] [Full Text] [PDF]