The Journal of Immunology, Vol 153, Issue 7 3218-3227, Copyright © 1994 by American Association of Immunologists

ARTICLES

Apoptotic neutrophils are phagocytosed by fibroblasts with participation of the fibroblast vitronectin receptor and involvement of a mannose/fucose-specific lectin

SE Hall, JS Savill, PM Henson and C Haslett
Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.

The fate of neutrophils (PMNs) at sites of inflammation is important to our understanding of many disease processes. Previously, it had been widely assumed that extravasated PMNs inevitably disintegrated before their fragments were removed by local phagocytes, but we have recently described an alternative process whereby senescent PMNs undergo apoptosis (programmed cell death). This process leads to macrophage (Mphi) ingestion of the intact cell by a novel phagocytic recognition process. In this study, we show that monolayers of fibroblasts also can selectively phagocytose apoptotic PMNs and that the recognition of apoptotic PMNs by fibroblasts involves two distinct mechanisms: one uses the vitronectin receptor, as in Mphi ingestion of PMNs; the other uses a mannose/fucose-specific lectin, which plays no part in Mphi phagocytosis of apoptotic PMNs. The direct interactions between PMNs and fibroblasts demonstrated herein may have implications for our understanding of the relationship between inflammation and scarring in many diseases.

This article has been cited by other articles:

				N. Malagolini, M. Chiricolo, M. Marini, and F. Dall'Olio Exposure of {alpha}2,6-sialylated lactosaminic chains marks apoptotic and necrotic death in different cell types Glycobiology, February 1, 2009; 19(2): 172 - 181. [Abstract] [Full Text] [PDF]

				J. C. Todt, B. Hu, and J. L. Curtis The scavenger receptor SR-A I/II (CD204) signals via the receptor tyrosine kinase Mertk during apoptotic cell uptake by murine macrophages J. Leukoc. Biol., August 1, 2008; 84(2): 510 - 518. [Abstract] [Full Text] [PDF]

				J. Monks, C. Smith-Steinhart, E. R. Kruk, V. A. Fadok, and P. M. Henson Epithelial Cells Remove Apoptotic Epithelial Cells During Post-Lactation Involution of the Mouse Mammary Gland Biol Reprod, April 1, 2008; 78(4): 586 - 594. [Abstract] [Full Text] [PDF]

				H. Yuita, M. Tsuiji, Y. Tajika, Y. Matsumoto, K. Hirano, N. Suzuki, and T. Irimura Retardation of removal of radiation-induced apoptotic cells in developing neural tubes in macrophage galactose-type C-type lectin-1-deficient mouse embryos Glycobiology, December 1, 2005; 15(12): 1368 - 1375. [Abstract] [Full Text] [PDF]

				K. Hirano, Y. Miki, Y. Hirai, R. Sato, T. Itoh, A. Hayashi, M. Yamanaka, S. Eda, and M. Beppu A Multifunctional Shuttling Protein Nucleolin Is a Macrophage Receptor for Apoptotic Cells J. Biol. Chem., November 25, 2005; 280(47): 39284 - 39293. [Abstract] [Full Text] [PDF]

				B. Hu, J. H. Jennings, J. Sonstein, J. Floros, J. C. Todt, T. Polak, and J. L. Curtis Resident Murine Alveolar and Peritoneal Macrophages Differ in Adhesion of Apoptotic Thymocytes Am. J. Respir. Cell Mol. Biol., May 1, 2004; 30(5): 687 - 693. [Abstract] [Full Text] [PDF]

				H. Yamasawa, K. Oshikawa, S. Ohno, and Y. Sugiyama Macrolides Inhibit Epithelial Cell-Mediated Neutrophil Survival by Modulating Granulocyte Macrophage Colony-Stimulating Factor Release Am. J. Respir. Cell Mol. Biol., April 1, 2004; 30(4): 569 - 575. [Abstract] [Full Text] [PDF]

				S. Eda, M. Yamanaka, and M. Beppu Carbohydrate-mediated Phagocytic Recognition of Early Apoptotic Cells Undergoing Transient Capping of CD43 Glycoprotein J. Biol. Chem., February 13, 2004; 279(7): 5967 - 5974. [Abstract] [Full Text] [PDF]

				J. D. Johnson, K. L. Hess, and J. M. Cook-Mills CD44, {alpha}4 integrin, and fucoidin receptor-mediated phagocytosis of apoptotic leukocytes J. Leukoc. Biol., November 1, 2003; 74(5): 810 - 820. [Abstract] [Full Text] [PDF]

				T. Hisatomi, T. Sakamoto, K.-h. Sonoda, C. Tsutsumi, H. Qiao, H. Enaida, I. Yamanaka, T. Kubota, T. Ishibashi, S. Kura, et al. Clearance of Apoptotic Photoreceptors: Elimination of Apoptotic Debris into the Subretinal Space and Macrophage-Mediated Phagocytosis via Phosphatidylserine Receptor and Integrin {alpha}v{beta}3 Am. J. Pathol., June 1, 2003; 162(6): 1869 - 1879. [Abstract] [Full Text] [PDF]

				Y. Moodley, P. Rigby, C. Bundell, S. Bunt, H. Hayashi, N. Misso, R. McAnulty, G. Laurent, A. Scaffidi, P. Thompson, et al. Macrophage Recognition and Phagocytosis of Apoptotic Fibroblasts Is Critically Dependent on Fibroblast-Derived Thrombospondin 1 and CD36 Am. J. Pathol., March 1, 2003; 162(3): 771 - 779. [Abstract] [Full Text] [PDF]

				P. Weinmann, K. Scharffetter-Kochanek, S. B. Forlow, T. Peters, and B. Walzog A role for apoptosis in the control of neutrophil homeostasis in the circulation: insights from CD18-deficient mice Blood, January 15, 2003; 101(2): 739 - 746. [Abstract] [Full Text] [PDF]

				M. J. Howard and C. M. Isacke The C-type Lectin Receptor Endo180 Displays Internalization and Recycling Properties Distinct from Other Members of the Mannose Receptor Family J. Biol. Chem., August 23, 2002; 277(35): 32320 - 32331. [Abstract] [Full Text] [PDF]

				S. Basu, G. Hodgson, M. Katz, and A. R. Dunn Evaluation of role of G-CSF in the production, survival, and release of neutrophils from bone marrow into circulation Blood, July 18, 2002; 100(3): 854 - 861. [Abstract] [Full Text] [PDF]

				Y. Ren, L. Stuart, F. P. Lindberg, A. R. Rosenkranz, Y. Chen, T. N. Mayadas, and J. Savill Nonphlogistic Clearance of Late Apoptotic Neutrophils by Macrophages: Efficient Phagocytosis Independent of {{beta}}2 Integrins J. Immunol., April 1, 2001; 166(7): 4743 - 4750. [Abstract] [Full Text] [PDF]

				T. L. Schagat, J. A. Wofford, and J. R. Wright Surfactant Protein A Enhances Alveolar Macrophage Phagocytosis of Apoptotic Neutrophils J. Immunol., February 15, 2001; 166(4): 2727 - 2733. [Abstract] [Full Text] [PDF]

				A. Moreno, M. L. Villar, C. Camara, R. Luque, C. Cespon, P. Gonzalez-Porque, G. Roy, J. Lopez-Jimenez, A. Bootello, and E. R. Santiago Interleukin-6 dimers produced by endothelial cells inhibit apoptosis of B-chronic lymphocytic leukemia cells Blood, January 1, 2001; 97(1): 242 - 249. [Abstract] [Full Text] [PDF]

				S. Couzinet, E. Cejas, J. Schittny, P. Deplazes, R. Weber, and S. Zimmerli Phagocytic Uptake of Encephalitozoon cuniculi by Nonprofessional Phagocytes Infect. Immun., December 1, 2000; 68(12): 6939 - 6945. [Abstract] [Full Text] [PDF]

				N. Platt, H. Suzuki, T. Kodama, and S. Gordon Apoptotic Thymocyte Clearance in Scavenger Receptor Class A-Deficient Mice Is Apparently Normal J. Immunol., May 1, 2000; 164(9): 4861 - 4867. [Abstract] [Full Text] [PDF]

				H Sheikh, H Yarwood, A Ashworth, and C. Isacke Endo180, an endocytic recycling glycoprotein related to the macrophage mannose receptor is expressed on fibroblasts, endothelial cells and macrophages and functions as a lectin receptor J. Cell Sci., January 3, 2000; 113(6): 1021 - 1032. [Abstract] [PDF]

				E. Rapoport and J. Pendu Glycosylation alterations ofcells in late phase apoptosis from colon carcinomas Glycobiology, December 1, 1999; 9(12): 1337 - 1345. [Abstract] [Full Text] [PDF]

				C. HASLETT Granulocyte Apoptosis and Its Role in the Resolution and Control of Lung Inflammation Am. J. Respir. Crit. Care Med., November 1, 1999; 160(5): S5 - 11. [Abstract] [Full Text] [PDF]

				G. M. Walsh, D. W. Sexton, M. G. Blaylock, and C. M. Convery Resting and Cytokine-Stimulated Human Small Airway Epithelial Cells Recognize and Engulf Apoptotic Eosinophils Blood, October 15, 1999; 94(8): 2827 - 2835. [Abstract] [Full Text] [PDF]

				O. D. Moffatt, A. Devitt, E. D. Bell, D. L. Simmons, and C. D. Gregory Macrophage Recognition of ICAM-3 on Apoptotic Leukocytes J. Immunol., June 1, 1999; 162(11): 6800 - 6810. [Abstract] [Full Text] [PDF]

				L. Holmgren, A. Szeles, E. Rajnavolgyi, J. Folkman, G. Klein, I. Ernberg, and K. I. Falk Horizontal Transfer of DNA by the Uptake of Apoptotic Bodies Blood, June 1, 1999; 93(11): 3956 - 3963. [Abstract] [Full Text] [PDF]

				P. Weinmann, P. Gaehtgens, and B. Walzog Bcl-Xl- and Bax-alpha -Mediated Regulation of Apoptosis of Human Neutrophils Via Caspase-3 Blood, May 1, 1999; 93(9): 3106 - 3115. [Abstract] [Full Text] [PDF]

				B. R. Schwartz, A. Karsan, T. Bombeli, and J. M. Harlan A Novel {beta}1 Integrin-Dependent Mechanism of Leukocyte Adherence to Apoptotic Cells J. Immunol., April 15, 1999; 162(8): 4842 - 4848. [Abstract] [Full Text] [PDF]

				C. M. SKOLD, X. LIU, T. UMINO, Y. ZHU, Y. OHKUNI, D. J. ROMBERGER, J. R. SPURZEM, A. J. HEIRES, and S. I. RENNARD Human Neutrophil Elastase Augments Fibroblast-Mediated Contraction of Released Collagen Gels Am. J. Respir. Crit. Care Med., April 1, 1999; 159(4): 1138 - 1146. [Abstract] [Full Text] [PDF]

				S. Reid, A. Ritchie, L. Boring, J. Gosling, S. Cooper, G. Hangoc, I. F. Charo, and H. E. Broxmeyer Enhanced Myeloid Progenitor Cell Cycling and Apoptosis in Mice Lacking the Chemokine Receptor, CCR2 Blood, March 1, 1999; 93(5): 1524 - 1533. [Abstract] [Full Text] [PDF]

				W. J. Arlein, J. D. Shearer, and M. D. Caldwell Continuity between wound macrophage and fibroblast phenotype: analysis of wound fibroblast phagocytosis Am J Physiol Regulatory Integrative Comp Physiol, October 1, 1998; 275(4): R1041 - R1048. [Abstract] [Full Text] [PDF]

				K. Oka, T. Sawamura, K.-i. Kikuta, S. Itokawa, N. Kume, T. Kita, and T. Masaki Lectin-like oxidized low-density lipoprotein receptor 1 mediates phagocytosis of aged/apoptotic cells in endothelial cells PNAS, August 4, 1998; 95(16): 9535 - 9540. [Abstract] [Full Text] [PDF]

				E R CHILVERS, A G ROSSI, J MURRAY, and C HASLETT Regulation of granulocyte apoptosis and implications for anti-inflammatory therapy Thorax, July 1, 1998; 53(7): 533 - 534. [Full Text]

				A. Haunstetter and S. Izumo Apoptosis : Basic Mechanisms and Implications for Cardiovascular Disease Circ. Res., June 15, 1998; 82(11): 1111 - 1129. [Full Text] [PDF]

				M. B. Lowry, A.-M. Duchemin, J. M. Robinson, and C. L. Anderson Functional Separation of Pseudopod Extension and Particle Internalization during Fc{gamma} Receptor-mediated Phagocytosis J. Exp. Med., January 19, 1998; 187(2): 161 - 176. [Abstract] [Full Text] [PDF]

				S.S. Srivatsa, L. A Fitzpatrick, P. W Tsao, T. M Reilly, D. R Holmes Jr, R. S Schwartz, and S. A Mousa Selective {alpha}v{beta}3 integrin blockade potently limits neointimal hyperplasia and lumen stenosis following deep coronary arterial stent injury:: Evidence for the functional importance of integrin {alpha}v{beta}3 and osteopontin expression during neointima formation Cardiovasc Res, December 1, 1997; 36(3): 408 - 428. [Abstract] [Full Text] [PDF]

				D. G. Perry, P. Wisniowski, G. L. Daugherty, J. Downing, and W. J. Martin II Nonimmune Phagocytosis of Liposomes by Rat Alveolar Macrophages Is Enhanced by Vitronectin and Is Vitronectin-receptor Mediated Am. J. Respir. Cell Mol. Biol., October 1, 1997; 17(4): 462 - 470. [Abstract] [Full Text]

				N. Uozumi, S. Yanagidani, E. Miyoshi, Y. Ihara, T. Sakuma, C.-X. Gao, T. Teshima, S. Fujii, T. Shiba, and N. Taniguchi Purification and cDNA Cloning of Porcine Brain GDP-L-Fuc:N-Acetyl-beta -D-Glucosaminide alpha 1right-arrow 6Fucosyltransferase J. Biol. Chem., November 1, 1996; 271(44): 27810 - 27817. [Abstract] [Full Text] [PDF]

				M.R. Bennett, D.F. Gibson, S.M. Schwartz, and J.F. Tait Binding and Phagocytosis of Apoptotic Vascular Smooth Muscle Cells Is Mediated in Part by Exposure of Phosphatidylserine Circ. Res., December 1, 1995; 77(6): 1136 - 1142. [Abstract] [Full Text]

				C. Thompson Apoptosis in the pathogenesis and treatment of disease Science, March 10, 1995; 267(5203): 1456 - 1462. [Abstract] [PDF]

				V. A. Fadok, A. de Cathelineau, D. L. Daleke, P. M. Henson, and D. L. Bratton Loss of Phospholipid Asymmetry and Surface Exposure of Phosphatidylserine Is Required for Phagocytosis of Apoptotic Cells by Macrophages and Fibroblasts J. Biol. Chem., January 5, 2001; 276(2): 1071 - 1077. [Abstract] [Full Text] [PDF]