Abstract
Abstract It has been recently shown that Fas ligand (FasL) expression on islet β grafts results in neutrophilic infiltration and graft rejection. In this study, we show that human recombinant soluble FasL is endowed with potent chemotactic properties toward human neutrophilic polymorphonuclear leukocytes (neutrophils) at concentrations incapable of inducing cell apoptosis. Furthermore, neutrophils exposed to soluble FasL did not display detectable change of intracellular Ca2+ and did not undergo superoxide production or exocytosis of primary and secondary granules. Our results show that FasL is a potent chemoattractant for human neutrophils without evoking their secretory responses. This finding suggests a novel proinflammatory function for this ligand and may help to clarify the mechanism governing FasL-mediated graft rejection, thereby offering rational bases for controlling and modulating FasL-based immunotherapies.
References
42
Referenced
136
-
Suda, T., T. Takahashi, P. Golstein, S. Nagata. 1993. Molecular cloning and expression of the Fas ligand, a novel member of the tumor necrosis factor family. Cell 75: 1169
(
10.1016/0092-8674(93)90326-L
) -
Nagata, S.. 1997. Apoptosis by death factor. Cell 88: 355
(
10.1016/S0092-8674(00)81874-7
) -
Kayagaki, N., A. Kawasaki, T. Ebata, H. Ohmoto, S. Ikeda, S. Inoue, K. Yoshino, K. Okumura, H. Yagita. 1995. Metalloproteinase-mediated release of human Fas ligand. J. Exp. Med. 182: 1777
(
10.1084/jem.182.6.1777
) -
Nagata, S., P. Golstein. 1995. The Fas death factor. Science 267: 1449
(
10.1126/science.7533326
) -
Hetts, S. W.. 1998. To die or not to die. JAMA 279: 300
(
10.1001/jama.279.4.300
) -
Griffith, T. S., T. Brunner, S. M. Fletchter, D. R. Green, T. A. Ferguson. 1995. Fas ligand-induced apoptosis as a mechanism of immune privilege. Science 270: 1189
(
10.1126/science.270.5239.1189
) -
Bellgrau, D., D. Gold, H. Selawry, J. Moore, A. Franzusoff, R. C. Duke. 1995. A role for CD95 ligand in preventing graft rejection. Nature 377: 630
(
10.1038/377630a0
) -
Lau, H. T., M. Yu, A. Fontana, C. I. Stoeckert, Jr. 1996. Prevention of islet allograft rejection with engineered myoblast expressing FasL in mice. Science 273: 109
(
10.1126/science.273.5271.109
) -
Kang, S. M., D. B. Schneider, Z. Lin, D. Hanahan, D. A. Dichek, P. G. Stock, S. Baekkeskov. 1997. Fas ligand expression in islets of Langerhans does not confer immune privilege and instead targets them for rapid destruction. Nat. Med. 3: 738
(
10.1038/nm0797-738
) -
Allison, J., H. M. Georgiou, A. Strasser, D. L. Vaux. 1997. Transgenic expression of CD95 ligand on islet β cells induces a granulocytic infiltration but does not confer immune privilege upon islet allografts. Proc. Natl. Acad. Sci. USA 94: 3943
(
10.1073/pnas.94.8.3943
) -
Seino, K. I., N. Kayagaki, K. Okumura, H. Yagita. 1997. Antitumor effect of locally produced CD95 ligand. Nat. Med. 3: 165
(
10.1038/nm0297-165
) -
Sekine, C., H. Yagita, T. Kobata, T. Hasunuma, K. Nishioka, K. Okumura. 1996. Fas-mediated stimulation induces IL-8 secretion by rheumatoid arthritis synoviocytes independently of CPP32-mediated apoptosis. Biochem. Biophys. Res. Commun. 228: 14
(
10.1006/bbrc.1996.1610
) -
Abreu-Martin, M. T., A. Vidrich, D. H. Lynch, S. R. Targan. 1995. Divergent induction of apoptosis and IL-8 secretion in HT-29 cells in response to TNF-α and ligation of Fas antigen. J. Immunol. 155: 4147
(
10.4049/jimmunol.155.9.4147
) -
Ottonello, L., P. Morone, P. Dapino, F. Dallegri. 1996. Monoclonal Lym-1 antibody-dependent lysis of B-lymphoblastoid tumor targets by human complement and cytokine-exposed mononuclear and neutrophilic polymorphonuclear leukocytes. Blood 87: 5171
(
10.1182/blood.V87.12.5171.bloodjournal87125171
) -
Dankberg, F., M. Perdinsky. 1976. A test of granulocyte membrane integrity and phagocyte function. Cryobiology 13: 430
(
10.1016/0011-2240(76)90098-5
) -
Corcione, A., L. Ottonello, G. Tortolina, P. Tasso, F. Ghiotto, I. Airoldi, G. Taborelli, F. Malavasi, F. Dallegri, V. Pistoia. 1997. Recombinant tumor necrosis factor enhances the locomotion of memory and naive B lymphocytes from human tonsils through the selective engagement of the type II receptor. Blood 90: 4493
(
10.1182/blood.V90.11.4493.4493_4493_4501
) -
Zigmond, S. H., J. G. Hirsch. 1973. Leukocyte locomotion and chemotaxis. J. Exp. Med. 137: 387
(
10.1084/jem.137.2.387
) - Metcalf, J. A., J. I. Gallin, W. M. Nauseef, R. K. Root. 1986. Laboratory Manual of Neutrophil Function Raven Press, New York.
-
Dallegri, F., F. Patrone, A. Ballestrero, G. Frumento, C. Sacchetti. 1986. Inhibition of neutrophil cytolysin production by target cells. Blood 67: 1265
(
10.1182/blood.V67.5.1265.1265
) -
Babior, B. M., R. S. Knipes, J. T. Curnutte. 1973. Biological defense mechanisms. The production by leukocytes of superoxide, a potential bactericidal agents. J. Clin. Invest. 52: 741
(
10.1172/JCI107236
) - Beutler, E.. 1984. Red Cell Metabolism: A Manual of Biochemical Methods 3rd Ed. Grune & Stratton, Orlando.
- Ottonello, L., R. Gonella, P. Dapino, C. Sacchetti, F. Dallegri. 1998. Prostaglandin E2 inhibits apoptosis in human neutrophilic polymorphonuclear leukocytes: role of intracellular cyclic AMP levels. Exp. Hematol. 26: 895
-
Wilkinson, P. C.. 1985. Random locomotion, chemotaxis and chemokinesis. Immunol. Today 6: 273
(
10.1016/0167-5699(85)90066-0
) - Wilkinson, P. C.. 1974. The role of chemotaxis in inflammatory reactions. P. C. Wilkinson, Jr, ed. Chemotaxis and Inflammation 149 Churchill Livingstone, London.
- Snyderman, R., R. J. Uhing. 1992. Chemoattractant stimulus-response coupling. J. I. Gallin, Jr, and I. M. Goldstein, Jr, and R. Snyderman, Jr, eds. Inflammation; Basic Principles and Clinical Correlates 421 Raven Press, New York.
- Wilkinson, P. C., R. B. Allan. 1978. Assay systems for measuring leukocyte locomotion: an overview. J. I. Gallin, Jr, and P. G. Quie, Jr, eds. Leukocyte Chemotaxis 1 Raven Press, New York.
-
Islam, L. N., I. C. McKay, P. C. Wilkinson. 1985. The use of collagen or fibrin gel for the assay of human neutrophil chemotaxis. J. Immunol. Methods 85: 137
(
10.1016/0022-1759(85)90282-0
) -
Seino, K., K. Iwabuchi, N. Kayagaki, R. Miyata, I. Nagaoka, A. Matsuzawa, K. Fukao, H. Yagita, K. Okumura. 1998. Chemotactic activity of soluble Fas ligand against phagocytes. J. Immunol. 161: 4484
(
10.4049/jimmunol.161.9.4484
) -
Reibman, J., S. Meixler, T. C. Lee, L. I. Gold, B. N. Cronstein, K. A. Haines, S. L. Kolasinski, G. Weissmann. 1991. Transforming growth factor β1, a potent chemoattractant for human neutrophils, bypasses classic signal-transduction pathways. Proc. Natl. Acad. Sci. USA 88: 6805
(
10.1073/pnas.88.15.6805
) - Stossel, T. P.. 1992. The mechanical responses of white blood cells. J. I. Gallin, Jr, and I. M. Goldstein, Jr, and R. Snyderman, Jr, eds. Inflammation: Basic Principles and Clinical Correlates 459 Raven Press, New York.
-
Meshulam, T., P. Proto, R. D. Diamond, D. A. Melnick. 1986. Calcium modulation and chemotactic response: divergent stimulation of neutrophil chemotaxis and cytosolic calcium response by the chemotactic peptide receptor. J. Immunol. 137: 1954
(
10.4049/jimmunol.137.6.1954
) -
Zigmond, S. H., J. L. Slonczewski, M. W. Wilde, M. Carson. 1988. Polymorphonuclear leukocyte locomotion is insensitive to lowered cytoplasmic calcium levels. Cell Motil. Cytoskeleton 137: 1954
(
10.1002/cm.970090210
) -
Fabbri, M., S. Spisani, C. Biondi, L. Barbin, M. L. Colamussi, A. Cariani, S. Traniello, I. Torrini, M. E. Ferretti. 1997. Two for-Met-Leu-Phe-OMe analogues trigger selective neutrophil responses: a differential effect on cytosolic free Ca2+. Biochim. Biophys. Acta 1359: 233
(
10.1016/S0167-4889(97)00101-8
) -
Haines, K. A., S. L. Kolasinski, B. N. Cronstein, J. Reibman, L. I. Gold, G. Weissmann. 1993. Chemoattraction of neutrophils by Substance P and transforming growth factor-β1 is inadequately explained by current models of lipid remodeling. J. Immunol. 151: 1491
(
10.4049/jimmunol.151.3.1491
) -
Kolasinski, S. L., K. A. Haines, E. L. Siegel, B. N. Cronstein, S. B. Abramson. 1992. Neuropeptides and inflammation: a somatostatin analog as a selective antagonist if neutrophil activation by Substance P. Arthritis Rheum. 35: 369
(
10.1002/art.1780350402
) -
Senior, R. M., W. F. Skogen, G. L. Griffin, G. D. Wilner. 1986. Effects of fibrinogen derivatives upon the inflammatory response: studies with human fibrinopeptide B. J. Clin. Invest. 77: 1014
(
10.1172/JCI112353
) - Rossi, A. G., P. G. Hellewell. 1994. Mechanisms of neutrophil accumulation in tissues. P. G. Hellewell, Jr, and T. J. Williams, Jr, eds. Immunopharmacology of Neutrophils 223 Academic Press, London.
-
Bazzoni, F., M. A. Cassatella, F. Rossi, M. Ceska, B. Dewald, M. Baggiolini. 1991. Phagocytosing neutrophils produce and release high amounts of the neutrophil-activating peptide 1/interleukin 8. J. Exp. Med. 173: 771
(
10.1084/jem.173.3.771
) -
Sisson, J. H., S. M. Prescott, T. M. McIntyre, G. A. Zimmerman. 1987. Production of platelet-activating factor by stimulated human polymorphonuclear leukocytes: correlation of synthesis with release, functional events, and leukotriene B4 metabolism. J. Immunol. 138: 3918
(
10.4049/jimmunol.138.11.3918
) - Lam, B. K., and K. F. Austen. 1992. Leukotrienes: biosynthesis, release and actions. In Inflammation: Basic Principles and Clinical Correlates. J. I. Gallin, I. M. Goldstein, and R. Snyderman, R., eds. Raven Press, New York, p. 139.
-
Liles, W. C., P. A. Kiener, J. A. Ledbetter, A. Aruffo, S. J. Klebanoff. 1996. Differential expression of Fas (CD95) and Fas ligand on normal human phagocytes: implications for the regulation of apoptosis in neutrophils. J. Exp. Med. 184: 429
(
10.1084/jem.184.2.429
) -
Hashimoto, H., M. Tanaka, T. Suda, T. Tomita, K. Hayashida, E. Takeuchi, M. Kaneko, H. Takano, S. Nagata, T. Ochi. 1998. Soluble Fas ligand in the joints of patients with rheumatoid arthritis and osteoarthritis. Arthritis Rheum. 41: 657
(
10.1002/1529-0131(199804)41:4<657::AID-ART12>3.0.CO;2-N
)
Dates
Type | When |
---|---|
Created | 2 years, 8 months ago (Dec. 31, 2022, 10:14 p.m.) |
Deposited | 8 months ago (Jan. 2, 2025, 1:15 p.m.) |
Indexed | 1 month, 2 weeks ago (July 14, 2025, 11:24 p.m.) |
Issued | 26 years, 5 months ago (March 15, 1999) |
Published | 26 years, 5 months ago (March 15, 1999) |
Published Print | 26 years, 5 months ago (March 15, 1999) |
@article{Ottonello_1999, title={Soluble Fas Ligand Is Chemotactic for Human Neutrophilic Polymorphonuclear Leukocytes}, volume={162}, ISSN={1550-6606}, url={http://dx.doi.org/10.4049/jimmunol.162.6.3601}, DOI={10.4049/jimmunol.162.6.3601}, number={6}, journal={The Journal of Immunology}, publisher={Oxford University Press (OUP)}, author={Ottonello, Luciano and Tortolina, Giuseppe and Amelotti, Massimo and Dallegri, Franco}, year={1999}, month=mar, pages={3601–3606} }