{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:26:01Z","timestamp":1791213961556,"version":"4.1.0"},"reference-count":44,"publisher":"American Society for Cell Biology (ASCB)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MBoC"],"published-print":{"date-parts":[[2004,6]]},"abstract":"<jats:p>When cells undergo apoptosis, or programmed cell death, they expose phosphatidylserine (PS) on their surface. Macrophages that efficiently phagocytose apoptotic cells also express PS on their surface, although at a lower level. The PS exposed on both cells is required for phagocytosis, because uptake is inhibited by masking PS on either cell with annexin V, a PS-binding protein. The inhibition is not additive, suggesting that the exposed PS molecules on the two cells participate in a common process. We asked whether this dual requirement reflects bridging of the target cell and macrophage by bivalent, PS-binding annexins. Monoclonal antibodies (mAbs) against annexins I or II stained a variety of live phagocytes. Apoptotic Jurkat T lymphocytes and human peripheral T lymphocytes, but not apoptotic thymocytes, were stained by anti-annexin I but not II. Phagocytosis of apoptotic targets was inhibited by mAbs to annexins I or II, or by pretreatment of macrophages with the same mAbs. Pretreatment of apoptotic thymocytes had no effect, whereas pretreating Jurkat cells with anti-annexin I or removing annexin I with EGTA was inhibitory. Annexin bridging is vectorial, because annexin is bound to PS molecules on targets but not on macrophages, suggesting annexins serve as both ligand and receptor in promoting phagocytosis.<\/jats:p>","DOI":"10.1091\/mbc.e03-09-0670","type":"journal-article","created":{"date-parts":[[2004,4,6]],"date-time":"2004-04-06T00:45:04Z","timestamp":1081212304000},"page":"2863-2872","source":"Crossref","is-referenced-by-count":106,"title":["Macrophage Surface Expression of Annexins I and II in the Phagocytosis of Apoptotic Lymphocytes"],"prefix":"10.1091","volume":"15","author":[{"given":"Xiaoxuan","family":"Fan","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Penn State University, University Park, Pennsylvania 16802"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Krahling","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Penn State University, University Park, Pennsylvania 16802"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Biology, Clarion University, Clarion, Pennsylvania 16214"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Williamson","sequence":"additional","affiliation":[{"name":"Department of Biology, Amherst College, Amherst, Massachusetts 01002"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Schlegel","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Penn State University, University Park, Pennsylvania 16802"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1076","reference":[{"key":"REF1","doi-asserted-by":"crossref","unstructured":"Arur, S., Uche, U.E., Rezaul, K., Fong, M., Scranton, V., Cowan, A.E., Mohler, W., and Han, D. (2003). Annexin I is an endogenous ligand that mediates apoptotic cell engulfment.Dev. Cell4, 587-598.","DOI":"10.1016\/S1534-5807(03)00090-X"},{"key":"REF2","doi-asserted-by":"crossref","unstructured":"Balasubramanian, K., and Schroit, A.J. (1998). Characterization of phosphatidylserine-dependent beta (2)-glycoprotein I macrophage interactions: implications for apoptotic cell clearance by phagocytes.J. Biol. Chem.273, 29272-29277.","DOI":"10.1074\/jbc.273.44.29272"},{"key":"REF3","doi-asserted-by":"crossref","unstructured":"Bitto, E., Li, M., Tikhonov, A.M., Schlossman, M.L., and Cho, W. (2000). Mechanism of annexin I-mediated membrane aggregation.Biochemistry39, 13469-13477.","DOI":"10.1021\/bi001275u"},{"key":"REF4","doi-asserted-by":"crossref","unstructured":"Callahan, M.K., Halleck, M.S., Krahling, S., Henderson, A.J., Williamson, P., and Schlegel, R.A. (2003). Phosphatidylserine expression and phagocytosis of apoptotic thymocytes during differentiation of monocytic cells.J. 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Immunopathol.76, 195-202.","DOI":"10.1006\/clin.1995.1115"},{"key":"REF33","doi-asserted-by":"crossref","unstructured":"Perretti, M., Christian, H., Wheller, S.K., Aiello, I., Mugridge, K.G., Morris, J.F., Flower, R.J., and Goulding, N.J. (2000). Annexin I is stored within gelatinase granules of human neutrophils and mobilized on the cell surface upon adhesion but not phagocytosis.Cell Biol. Int.24, 163-174.","DOI":"10.1006\/cbir.1999.0468"},{"key":"REF34","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.8.5.767"},{"key":"REF35","doi-asserted-by":"crossref","unstructured":"Rosengarth, A., Gerke, V, and Luecke, H. (2001). X-ray structure of full-length annexin I and implications for membrane aggregation.J. Mol. Biol.306, 489-498.","DOI":"10.1006\/jmbi.2000.4423"},{"key":"REF36","doi-asserted-by":"crossref","unstructured":"Schlegel, R.A., Reed, J.A., McEvoy, L., Algarin, L., and Williamson, P. (1987). Phospholipid asymmetry of loaded red cells.Methods Enzymol.149, 281-293.","DOI":"10.1016\/0076-6879(87)49066-6"},{"key":"REF37","doi-asserted-by":"crossref","unstructured":"Schlegel, R.A., and Williamson, P. (2001). Phosphatidylserine, a death knell.Cell Death Differ.8, 551-563.","DOI":"10.1038\/sj.cdd.4400817"},{"key":"REF38","doi-asserted-by":"crossref","unstructured":"Seemann, J., Weber, K., and Gerke, V. (1996). Structural requirements for annexin 1-S100C complex formation.Biochem. J.319, 123-129.","DOI":"10.1042\/bj3190123"},{"key":"REF39","doi-asserted-by":"crossref","unstructured":"Siever, D.A., and Erickson, H.P. (1997). Extracellular annexin II.Int. J. Biochem. Cell Biol.29, 1219-1223.","DOI":"10.1016\/S1357-2725(97)00057-5"},{"key":"REF40","doi-asserted-by":"crossref","unstructured":"Tressler, R.J., Updyke, T.V., Yeatman, T., and Nicolson, G.L. (1993). Extracellular annexin II is associated with divalent cation-dependent tumor cell\u2013endothelial cell adhesion of metastatic RAW117 large-cell lymphoma cells.J. Cell Biochem.53, 265-276.","DOI":"10.1002\/jcb.240530311"},{"key":"REF41","doi-asserted-by":"crossref","unstructured":"van den Eijnde, S.M., Boshart, L., Reutelingsperger, C.P.M., De Zeeuw, C.I., and Vermeij-Keers, C. (1997). Phosphatidylserine plasma membrane asymmetry in vivo: a pancellular phenomenon which alters during apoptosis.Cell Death Differ.4, 311-316.","DOI":"10.1038\/sj.cdd.4400241"},{"key":"REF42","doi-asserted-by":"crossref","unstructured":"Vergnolle, N., Comera, C., and Bueno, L. (1995). Annexin I is overexpressed and specifically secreted during experimentally-induced colitis in rats.Eur. J. Biochem.232, 603-610.","DOI":"10.1111\/j.1432-1033.1995.tb20850.x"},{"key":"REF43","doi-asserted-by":"crossref","unstructured":"Verhoven, B., Schlegel, R.A., and Williamson, P. (1995). Mechanisms of phosphatidylserine exposure, a phagocyte recognition signal, on apoptotic T lymphocytes.J. Exp. Med.82, 1597-1601.","DOI":"10.1084\/jem.182.5.1597"},{"key":"REF44","doi-asserted-by":"crossref","unstructured":"Williamson, P., Kulick, A., Zachowski, A., Schlegel, R.A., and Devaux, P.F. (1992). Ca2+induces transbilayer redistribution of all major phospholipids in human erythrocytes.Biochemistry31, 6355-6360.","DOI":"10.1021\/bi00142a027"}],"container-title":["Molecular Biology of the Cell"],"original-title":[],"language":"en","deposited":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T06:45:19Z","timestamp":1682664319000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.molbiolcell.org\/doi\/10.1091\/mbc.e03-09-0670"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,6]]},"references-count":44,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2004,6]]}},"alternative-id":["10.1091\/mbc.e03-09-0670"],"URL":"https:\/\/doi.org\/10.1091\/mbc.e03-09-0670","relation":{},"ISSN":["1059-1524","1939-4586"],"issn-type":[{"value":"1059-1524","type":"print"},{"value":"1939-4586","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,6]]}}}