DOI: 10.1084/jem.192.9.1353. C-Reactive Protein Binds to Apoptotic Cells, Protects the Cells from Assembly of the Terminal Complement Components, and Sustains an Antiinflammatory Innate Immune Response

C-Reactive Protein Binds to Apoptotic Cells, Protects the Cells from Assembly of the Terminal Complement Components, and Sustains an Antiinflammatory Innate Immune Response

10.1084/jem.192.9.1353

Crossref journal-article

Rockefeller University Press

The Journal of Experimental Medicine (291)

Abstract

C-reactive protein (CRP) is a serum protein that is massively induced as part of the innate immune response to infection and tissue injury. As CRP has been detected in damaged tissues and is known to activate complement, we assessed whether apoptotic lymphocytes bound CRP and determined the effect of binding on innate immunity. CRP bound to apoptotic cells in a Ca2+-dependent manner and augmented the classical pathway of complement activation but protected the cells from assembly of the terminal complement components. Furthermore, CRP enhanced opsonization and phagocytosis of apoptotic cells by macrophages associated with the expression of the antiinflammatory cytokine transforming growth factor β. The antiinflammatory effects of CRP required C1q and factor H and were not effective once cells had become necrotic. These observations demonstrate that CRP and the classical complement components act in concert to promote noninflammatory clearance of apoptotic cells and may help to explain how deficiencies of the classical pathway and certain pentraxins lead to impaired handling of apoptotic cells and increased necrosis with the likelihood of immune response to self.

Bibliography

Gershov, D., Kim, S., Brot, N., & Elkon, K. B. (2000). C-Reactive Protein Binds to Apoptotic Cells, Protects the Cells from Assembly of the Terminal Complement Components, and Sustains an Antiinflammatory Innate Immune Response. The Journal of Experimental Medicine, 192(9), 1353â1364.

Authors 4

Debra Gershov (first)
SunJung Kim (additional)
Nathan Brot (additional)
Keith B. Elkon (additional)

References 61 Referenced 544

10.1038/sj.cdd.4400407 / Cell. Death. Differ. / Apoptosisthe importance of being eaten by Ren (1998)
10.1016/S0952-7915(99)00047-3 / Curr. Opin. Immunol. / CD14-dependent clearance of apoptotic cellsrelevance to the immune system by Gregory (2000)
{'key': '2023072509420834200_R3', 'first-page': '345', 'article-title': 'C-reactive protein and the acute phase response', 'volume': '27', 'author': 'Gewurz', 'year': '1982', 'journal-title': 'Adv. Int. Med.'} / Adv. Int. Med. / C-reactive protein and the acute phase response by Gewurz (1982)
10.1016/0167-5699(94)90138-4 / Immunol. Today. / The major acute phase reactantsC-reactive protein, serum amyloid P component and serum amyloid A protein by Steel (1994)
10.1007/BF02786357 / Immunol. Res. / C-reactive protein. Structural biology, gene expression and host defense function by Szalai (1997)
10.1084/jem.188.12.2313 / J. Exp. Med. / Complement-dependent clearance of apoptotic cells by human macrophages by Mevorach (1998)
10.1038/9544 / Nat. Med. / Serum amyloid P component controls chromatin degradation and prevents antinuclear autoimmunity by Bickerstaff (1999)
10.1084/jem.156.4.1268 / J. Exp. Med. / The acute phase response in (NZB × NZW)F1 and MRL/1 mice by Rordorf (1982)
10.1016/0167-5699(91)90003-C / Immunol. Today. / Complement deficiency and disease by Morgan (1991)
10.1038/ng0598-56 / Nat. Genet. / Homozygous C1q deficiency causes glomerulonephritis associated with multiple apoptotic bodies by Botto (1998)
10.4049/jimmunol.145.2.636 / J. Immunol. / Epitope mapping of recombinant HeLa SmB and B′ peptides obtained by the polymerase chain reaction by Elkon (1990)
10.1084/jem.162.2.459 / J. Exp. Med. / Lupus autoantibodies target the ribosomal P proteins by Elkon (1985)
10.1038/15200 / Nat. Med. / Natural adjuvantsendogenous activators of dendritic cells by Gallucci (1999)
10.1038/281155a0 / Nature. / Interaction of C-reactive protein with artificial phosphatidylcholine bilayers by Volanakis (1979)
10.1172/JCI5121 / J. Clin. Invest. / Molecular basis for the apoptotic defects in patients with CD95 (Fas/Apo-1) mutations by Vaishnaw (1999)
10.1002/(SICI)1097-0320(19970201)27:2<145::AID-CYTO6>3.0.CO;2-F / Cytometry. / A novel flow cytometric method for quantifying phagocytosis of apoptotic cells by Hess (1997)
{'key': '2023072509420834200_R17'}
10.4049/jimmunol.158.10.4525 / J. Immunol. / C1q binds directly and specifically to surface blebs of apoptotic human keratinocytes by Korb (1997)
10.1042/bj2640001 / Biochem. J. / Complement membrane attack on nucleated cellsresistance, recovery and non-lethal effects by Morgan (1989)
10.1084/jem.182.5.1545 / J. Exp. Med. / Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulusInhibition by overexpression of Bcl-2 and Ab1 by Martin (1995)
10.1084/jem.182.5.1597 / J. Exp. Med. / Mechanisms of phosphatidylserine exposure, a phagocyte recognition signal, on apoptotic T lymphocytes by Verhoven (1995)
10.4049/jimmunol.143.8.2553 / J. Immunol. / C-reactive protein reacts with the U1 small nuclear ribonucleoprotein by DuClos (1989)
10.1016/S0021-9258(17)39873-3 / J. Biol. Chem. / Binding of C-reactive protein to chromatin and nucleosome core particles by Robey (1984)
10.1007/BF00351177 / Mol. Biol. Rep. / The interaction of C-reactive protein and serum amyloid P component with nuclear antigens by Du Clos (1996)
10.1084/jem.179.4.1317 / J. Exp. Med. / Autoantigens targeted in systemic lupus erythematosus are clustered in two populations of surface structures on apoptotic keratinocytes by Casciola-Rosen (1994)
10.4049/jimmunol.146.7.2324 / J. Immunol. / Binding and complement activation by C-reactive protein via the collagen-like region of C1q and inhibition of these reactions by monoclonal antibodies to C-reactive protein and C1q by Jiang (1991)
10.4049/jimmunol.112.6.2135 / J. Immunol. / Interaction of C-reactive protein complexes with the complement system. I. Consumption of human complement associated with the reaction of C-reactive protein with pneumococcal C-polysaccharide and with the choline phosphatides, lecithin and sphingomyelin by Kaplan (1974)
10.1084/jem.140.3.631 / J. Exp. Med. / Interactions of C-reactive protein with the complement system. I. Protamine-induced consumption of complement in acute phase sera by Siegel (1974)
10.4049/jimmunol.136.4.1354 / J. Immunol. / Binding of C-reactive protein to nucleated cells leads to complement activation without cytolysis by Berman (1986)
{'key': '2023072509420834200_R30', 'first-page': '83', 'article-title': 'Regulation of the alternative pathway complement activation by an interaction of C-reactive protein with factor H', 'volume': '3', 'author': 'Aronen', 'year': '1993', 'journal-title': 'Immunol. Infect. Dis.'} / Immunol. Infect. Dis. / Regulation of the alternative pathway complement activation by an interaction of C-reactive protein with factor H by Aronen (1993)
10.1016/S0161-5890(98)90593-4 / Mol. Immunol. / Regulation of complement by direct binding of factor H to C-reactive protein by Mold (1998)
{'key': '2023072509420834200_R32', 'first-page': '147', 'article-title': 'Factor H', 'volume': '153', 'author': 'Vik', 'year': '1990', 'journal-title': 'Curr. Top. Microbiol. Immunol.'} / Curr. Top. Microbiol. Immunol. / Factor H by Vik (1990)
10.1172/JCI1112 / J. Clin. Invest. / Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF by Fadok (1998)
10.1038/37022 / Nature. / Immunosuppressive effects of apoptotic cells by Voll (1997)
10.1084/jem.191.3.411 / J. Exp. Med. / The induction of tolerance by dendritic cells that have captured apoptotic cells by Steinman (2000)
{'key': '2023072509420834200_R36', 'first-page': '911', 'article-title': 'Human monocyte derived macrophage phagocytosis of senescent eosinophils undergoing apoptosis', 'volume': '149', 'author': 'Stern', 'year': '1996', 'journal-title': 'Am. J. Pathol.'} / Am. J. Pathol. / Human monocyte derived macrophage phagocytosis of senescent eosinophils undergoing apoptosis by Stern (1996)
10.1084/jem.52.4.561 / J. Exp. Med. / Serological reactions in pneumonia with a non-protein fraction of pneumococcus by Tillett (1930)
10.1111/j.1749-6632.1982.tb22125.x / Ann. NY Acad. Sci. / Phylogenetic aspects of C-reactive protein and related proteins by Baltz (1982)
10.1016/S0969-2126(99)80023-9 / Structure. / The physiological structure of human C-reactive protein and its complex with phosphocholine by Thompson (1999)
10.1084/jem.114.6.961 / J. Exp. Med. / Studies of acute phase protein by Kushner (1961)
10.1016/0022-1759(95)00072-I / J. Immunol. Methods. / A novel assay for apoptosisflow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein-labeled annexin V by Vermes (1995)
10.1016/S0167-5699(97)01002-5 / Immunol. Today. / A role for secretory phospholipase A2 and C-reactive protein in the removal of injured cells by Hack (1997)
10.1084/jem.161.3.617 / J. Exp. Med. / Ligated complement receptors do not activate the arachidonic acid cascade in resident peritoneal macrophages by Aderem (1985)
10.1084/jem.158.6.2016 / J. Exp. Med. / Receptors for C3b and C3bi promote phagocytosis but not the release of toxic oxygen from human phagocytes by Wright (1983)
10.1084/jem.159.2.405 / J. Exp. Med. / Dissociation of phagocytosis from stimulation of the oxidative metabolic burst in macrophages by Yamamoto (1984)
10.1016/0167-5699(96)30013-3 / Immunol. Today. / Integrins as promiscuous signal transduction devices by Petty (1996)
10.1126/science.282.5394.1717 / Science. / Identification of two distinct mechanisms of phagocytosis controlled by different Rho GTPases by Caron (1998)
{'key': '2023072509420834200_R48'}
10.1615/CritRevImmunol.v19.i3.10 / Crit. Rev. Immunol. / Regulation of the complement membrane attack pathway by Morgan (1999)
10.4049/jimmunol.127.5.2089 / J. Immunol. / Inhibitory effect of C-reactive protein on alternative C pathway activation by liposomes and streptococcus pneumoniae by Mold (1981)
10.1016/S0162-3109(99)00007-7 / Immunopharmacology. / Regulation of complement activation by C-reactive protein by Mold (1999)
10.1084/jem.190.12.1733 / J. Exp. Med. / C-reactive protein and complement are important mediators of tissue damage in acute myocardial infarction by Griselli (1999)
10.1084/jem.190.4.585 / J. Exp. Med. / The major receptor for C-reactive protein on leukocytes is Fcγ receptor II by Bharadwaj (1999)
10.1172/JCI7817 / J. Clin. Invest. / C-reactive protein binding to FcγRIIa on human monocytes and neutrophils is allele-specific by Stein (2000)
10.1172/JCI118202 / J. Clin. Invest. / Apoptosis in rheumatoid arthritis synovium by Firestein (1995)
10.1002/art.1780380405 / Arthritis. Rheum. / Apoptosis and functional Fas antigen in rheumatoid arthritis synoviocytes by Nakajima (1995)
10.1097/00019501-199809050-00007 / Coron. Artery. Dis. / The variable morphological coexistence of apoptosis and necrosis in human myocardial infarctionsignificance for understanding its pathogenesis, clinical course, diagnosis and prognosis by James (1998)
10.1046/j.1471-4159.2000.0750819.x / J. Neurochem. / Correlation between caspase-3 activation and three different markers of DNA damage in neonatal cerebral hypoxia-ischemia by Zhu (2000)
10.1097/00005792-198105000-00004 / Medicine. / Immune complexes, complement, and anti-DNA in exacerbations of systemic lupus erythematosus by Lloyd (1981)
10.1016/S0140-6736(82)90321-X / Lancet. / Serum amyloid-A concentration in inflammatory diseases and its relationship to the incidence of reactive systemic amyloidosis by De Beer (1982)
10.1016/S0171-2985(98)80032-6 / Immunobiology. / C1q deficiencies and C1q in autoimmunity by Walport (1998)

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 12:48 p.m.)
Deposited	2 years, 1 month ago (July 25, 2023, 6:53 a.m.)
Indexed	6 days, 1 hour ago (Aug. 26, 2025, 3:10 a.m.)
Issued	24 years, 9 months ago (Nov. 6, 2000)
Published	24 years, 9 months ago (Nov. 6, 2000)
Published Online	24 years, 9 months ago (Nov. 6, 2000)
Published Print	24 years, 9 months ago (Nov. 6, 2000)

Funders 0

None

BibTeX

@article{Gershov_2000, title={C-Reactive Protein Binds to Apoptotic Cells, Protects the Cells from Assembly of the Terminal Complement Components, and Sustains an Antiinflammatory Innate Immune Response}, volume={192}, ISSN={1540-9538}, url={http://dx.doi.org/10.1084/jem.192.9.1353}, DOI={10.1084/jem.192.9.1353}, number={9}, journal={The Journal of Experimental Medicine}, publisher={Rockefeller University Press}, author={Gershov, Debra and Kim, SunJung and Brot, Nathan and Elkon, Keith B.}, year={2000}, month=nov, pages={1353–1364} }

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      "article-title": "CD14-dependent clearance of apoptotic cellsrelevance to the immune system",
      "volume": "12",
      "author": "Gregory",
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      "journal-title": "Curr. Opin. Immunol."
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      "key": "2023072509420834200_R3",
      "first-page": "345",
      "article-title": "C-reactive protein and the acute phase response",
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      "DOI": "10.1016/0167-5699(94)90138-4",
      "article-title": "The major acute phase reactantsC-reactive protein, serum amyloid P component and serum amyloid A protein",
      "volume": "15",
      "author": "Steel",
      "year": "1994",
      "journal-title": "Immunol. Today."
    },
    {
      "key": "2023072509420834200_R5",
      "doi-asserted-by": "crossref",
      "first-page": "127",
      "DOI": "10.1007/BF02786357",
      "article-title": "C-reactive protein. Structural biology, gene expression and host defense function",
      "volume": "16",
      "author": "Szalai",
      "year": "1997",
      "journal-title": "Immunol. Res."
    },
    {
      "key": "2023072509420834200_R6",
      "doi-asserted-by": "crossref",
      "first-page": "2313",
      "DOI": "10.1084/jem.188.12.2313",
      "article-title": "Complement-dependent clearance of apoptotic cells by human macrophages",
      "volume": "188",
      "author": "Mevorach",
      "year": "1998",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509420834200_R7",
      "doi-asserted-by": "crossref",
      "first-page": "694",
      "DOI": "10.1038/9544",
      "article-title": "Serum amyloid P component controls chromatin degradation and prevents antinuclear autoimmunity",
      "volume": "5",
      "author": "Bickerstaff",
      "year": "1999",
      "journal-title": "Nat. Med."
    },
    {
      "key": "2023072509420834200_R8",
      "doi-asserted-by": "crossref",
      "first-page": "1268",
      "DOI": "10.1084/jem.156.4.1268",
      "article-title": "The acute phase response in (NZB \u00d7 NZW)F1 and MRL/1 mice",
      "volume": "156",
      "author": "Rordorf",
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      "volume": "143",
      "author": "DuClos",
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      "volume": "259",
      "author": "Robey",
      "year": "1984",
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    },
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      "key": "2023072509420834200_R24",
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      "volume": "23",
      "author": "Du Clos",
      "year": "1996",
      "journal-title": "Mol. Biol. Rep."
    },
    {
      "key": "2023072509420834200_R25",
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      "first-page": "1317",
      "DOI": "10.1084/jem.179.4.1317",
      "article-title": "Autoantigens targeted in systemic lupus erythematosus are clustered in two populations of surface structures on apoptotic keratinocytes",
      "volume": "179",
      "author": "Casciola-Rosen",
      "year": "1994",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509420834200_R26",
      "doi-asserted-by": "crossref",
      "first-page": "2324",
      "DOI": "10.4049/jimmunol.146.7.2324",
      "article-title": "Binding and complement activation by C-reactive protein via the collagen-like region of C1q and inhibition of these reactions by monoclonal antibodies to C-reactive protein and C1q",
      "volume": "146",
      "author": "Jiang",
      "year": "1991",
      "journal-title": "J. Immunol."
    },
    {
      "key": "2023072509420834200_R27",
      "doi-asserted-by": "crossref",
      "first-page": "2135",
      "DOI": "10.4049/jimmunol.112.6.2135",
      "article-title": "Interaction of C-reactive protein complexes with the complement system. I. Consumption of human complement associated with the reaction of C-reactive protein with pneumococcal C-polysaccharide and with the choline phosphatides, lecithin and sphingomyelin",
      "volume": "112",
      "author": "Kaplan",
      "year": "1974",
      "journal-title": "J. Immunol."
    },
    {
      "key": "2023072509420834200_R28",
      "doi-asserted-by": "crossref",
      "first-page": "631",
      "DOI": "10.1084/jem.140.3.631",
      "article-title": "Interactions of C-reactive protein with the complement system. I. Protamine-induced consumption of complement in acute phase sera",
      "volume": "140",
      "author": "Siegel",
      "year": "1974",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509420834200_R29",
      "doi-asserted-by": "crossref",
      "first-page": "1354",
      "DOI": "10.4049/jimmunol.136.4.1354",
      "article-title": "Binding of C-reactive protein to nucleated cells leads to complement activation without cytolysis",
      "volume": "136",
      "author": "Berman",
      "year": "1986",
      "journal-title": "J. Immunol."
    },
    {
      "key": "2023072509420834200_R30",
      "first-page": "83",
      "article-title": "Regulation of the alternative pathway complement activation by an interaction of C-reactive protein with factor H",
      "volume": "3",
      "author": "Aronen",
      "year": "1993",
      "journal-title": "Immunol. Infect. Dis."
    },
    {
      "key": "2023072509420834200_R31",
      "doi-asserted-by": "crossref",
      "first-page": "346",
      "DOI": "10.1016/S0161-5890(98)90593-4",
      "article-title": "Regulation of complement by direct binding of factor H to C-reactive protein",
      "volume": "35",
      "author": "Mold",
      "year": "1998",
      "journal-title": "Mol. Immunol."
    },
    {
      "key": "2023072509420834200_R32",
      "first-page": "147",
      "article-title": "Factor H",
      "volume": "153",
      "author": "Vik",
      "year": "1990",
      "journal-title": "Curr. Top. Microbiol. Immunol."
    },
    {
      "key": "2023072509420834200_R33",
      "doi-asserted-by": "crossref",
      "first-page": "890",
      "DOI": "10.1172/JCI1112",
      "article-title": "Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF",
      "volume": "101",
      "author": "Fadok",
      "year": "1998",
      "journal-title": "J. Clin. Invest."
    },
    {
      "key": "2023072509420834200_R34",
      "doi-asserted-by": "crossref",
      "first-page": "350",
      "DOI": "10.1038/37022",
      "article-title": "Immunosuppressive effects of apoptotic cells",
      "volume": "390",
      "author": "Voll",
      "year": "1997",
      "journal-title": "Nature."
    },
    {
      "key": "2023072509420834200_R35",
      "doi-asserted-by": "crossref",
      "first-page": "411",
      "DOI": "10.1084/jem.191.3.411",
      "article-title": "The induction of tolerance by dendritic cells that have captured apoptotic cells",
      "volume": "191",
      "author": "Steinman",
      "year": "2000",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509420834200_R36",
      "first-page": "911",
      "article-title": "Human monocyte derived macrophage phagocytosis of senescent eosinophils undergoing apoptosis",
      "volume": "149",
      "author": "Stern",
      "year": "1996",
      "journal-title": "Am. J. Pathol."
    },
    {
      "key": "2023072509420834200_R37",
      "doi-asserted-by": "crossref",
      "first-page": "561",
      "DOI": "10.1084/jem.52.4.561",
      "article-title": "Serological reactions in pneumonia with a non-protein fraction of pneumococcus",
      "volume": "52",
      "author": "Tillett",
      "year": "1930",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509420834200_R38",
      "doi-asserted-by": "crossref",
      "first-page": "49",
      "DOI": "10.1111/j.1749-6632.1982.tb22125.x",
      "article-title": "Phylogenetic aspects of C-reactive protein and related proteins",
      "volume": "389",
      "author": "Baltz",
      "year": "1982",
      "journal-title": "Ann. NY Acad. Sci."
    },
    {
      "key": "2023072509420834200_R39",
      "doi-asserted-by": "crossref",
      "first-page": "169",
      "DOI": "10.1016/S0969-2126(99)80023-9",
      "article-title": "The physiological structure of human C-reactive protein and its complex with phosphocholine",
      "volume": "7",
      "author": "Thompson",
      "year": "1999",
      "journal-title": "Structure."
    },
    {
      "key": "2023072509420834200_R40",
      "doi-asserted-by": "crossref",
      "first-page": "961",
      "DOI": "10.1084/jem.114.6.961",
      "article-title": "Studies of acute phase protein",
      "volume": "114",
      "author": "Kushner",
      "year": "1961",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509420834200_R41",
      "doi-asserted-by": "crossref",
      "first-page": "39",
      "DOI": "10.1016/0022-1759(95)00072-I",
      "article-title": "A novel assay for apoptosisflow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein-labeled annexin V",
      "volume": "184",
      "author": "Vermes",
      "year": "1995",
      "journal-title": "J. Immunol. Methods."
    },
    {
      "key": "2023072509420834200_R42",
      "doi-asserted-by": "crossref",
      "first-page": "111",
      "DOI": "10.1016/S0167-5699(97)01002-5",
      "article-title": "A role for secretory phospholipase A2 and C-reactive protein in the removal of injured cells",
      "volume": "18",
      "author": "Hack",
      "year": "1997",
      "journal-title": "Immunol. Today."
    },
    {
      "key": "2023072509420834200_R43",
      "doi-asserted-by": "crossref",
      "first-page": "617",
      "DOI": "10.1084/jem.161.3.617",
      "article-title": "Ligated complement receptors do not activate the arachidonic acid cascade in resident peritoneal macrophages",
      "volume": "161",
      "author": "Aderem",
      "year": "1985",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509420834200_R44",
      "doi-asserted-by": "crossref",
      "first-page": "2016",
      "DOI": "10.1084/jem.158.6.2016",
      "article-title": "Receptors for C3b and C3bi promote phagocytosis but not the release of toxic oxygen from human phagocytes",
      "volume": "158",
      "author": "Wright",
      "year": "1983",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509420834200_R45",
      "doi-asserted-by": "crossref",
      "first-page": "405",
      "DOI": "10.1084/jem.159.2.405",
      "article-title": "Dissociation of phagocytosis from stimulation of the oxidative metabolic burst in macrophages",
      "volume": "159",
      "author": "Yamamoto",
      "year": "1984",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509420834200_R46",
      "doi-asserted-by": "crossref",
      "first-page": "209",
      "DOI": "10.1016/0167-5699(96)30013-3",
      "article-title": "Integrins as promiscuous signal transduction devices",
      "volume": "17",
      "author": "Petty",
      "year": "1996",
      "journal-title": "Immunol. Today."
    },
    {
      "key": "2023072509420834200_R47",
      "doi-asserted-by": "crossref",
      "first-page": "1717",
      "DOI": "10.1126/science.282.5394.1717",
      "article-title": "Identification of two distinct mechanisms of phagocytosis controlled by different Rho GTPases",
      "volume": "282",
      "author": "Caron",
      "year": "1998",
      "journal-title": "Science."
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    {
      "key": "2023072509420834200_R48"
    },
    {
      "key": "2023072509420834200_R49",
      "doi-asserted-by": "crossref",
      "first-page": "173",
      "DOI": "10.1615/CritRevImmunol.v19.i3.10",
      "article-title": "Regulation of the complement membrane attack pathway",
      "volume": "19",
      "author": "Morgan",
      "year": "1999",
      "journal-title": "Crit. Rev. Immunol."
    },
    {
      "key": "2023072509420834200_R50",
      "doi-asserted-by": "crossref",
      "first-page": "2089",
      "DOI": "10.4049/jimmunol.127.5.2089",
      "article-title": "Inhibitory effect of C-reactive protein on alternative C pathway activation by liposomes and streptococcus pneumoniae",
      "volume": "127",
      "author": "Mold",
      "year": "1981",
      "journal-title": "J. Immunol."
    },
    {
      "key": "2023072509420834200_R51",
      "doi-asserted-by": "crossref",
      "first-page": "23",
      "DOI": "10.1016/S0162-3109(99)00007-7",
      "article-title": "Regulation of complement activation by C-reactive protein",
      "volume": "42",
      "author": "Mold",
      "year": "1999",
      "journal-title": "Immunopharmacology."
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    {
      "key": "2023072509420834200_R52",
      "doi-asserted-by": "crossref",
      "first-page": "1733",
      "DOI": "10.1084/jem.190.12.1733",
      "article-title": "C-reactive protein and complement are important mediators of tissue damage in acute myocardial infarction",
      "volume": "190",
      "author": "Griselli",
      "year": "1999",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509420834200_R53",
      "doi-asserted-by": "crossref",
      "first-page": "585",
      "DOI": "10.1084/jem.190.4.585",
      "article-title": "The major receptor for C-reactive protein on leukocytes is Fc\u03b3 receptor II",
      "volume": "190",
      "author": "Bharadwaj",
      "year": "1999",
      "journal-title": "J. Exp. Med."
    },
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      "key": "2023072509420834200_R54",
      "doi-asserted-by": "crossref",
      "first-page": "369",
      "DOI": "10.1172/JCI7817",
      "article-title": "C-reactive protein binding to Fc\u03b3RIIa on human monocytes and neutrophils is allele-specific",
      "volume": "105",
      "author": "Stein",
      "year": "2000",
      "journal-title": "J. Clin. Invest."
    },
    {
      "key": "2023072509420834200_R55",
      "doi-asserted-by": "crossref",
      "first-page": "1631",
      "DOI": "10.1172/JCI118202",
      "article-title": "Apoptosis in rheumatoid arthritis synovium",
      "volume": "96",
      "author": "Firestein",
      "year": "1995",
      "journal-title": "J. Clin. Invest."
    },
    {
      "key": "2023072509420834200_R56",
      "doi-asserted-by": "crossref",
      "first-page": "485",
      "DOI": "10.1002/art.1780380405",
      "article-title": "Apoptosis and functional Fas antigen in rheumatoid arthritis synoviocytes",
      "volume": "38",
      "author": "Nakajima",
      "year": "1995",
      "journal-title": "Arthritis. Rheum."
    },
    {
      "key": "2023072509420834200_R57",
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      "first-page": "291",
      "DOI": "10.1097/00019501-199809050-00007",
      "article-title": "The variable morphological coexistence of apoptosis and necrosis in human myocardial infarctionsignificance for understanding its pathogenesis, clinical course, diagnosis and prognosis",
      "volume": "9",
      "author": "James",
      "year": "1998",
      "journal-title": "Coron. Artery. Dis."
    },
    {
      "key": "2023072509420834200_R58",
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      "first-page": "819",
      "DOI": "10.1046/j.1471-4159.2000.0750819.x",
      "article-title": "Correlation between caspase-3 activation and three different markers of DNA damage in neonatal cerebral hypoxia-ischemia",
      "volume": "75",
      "author": "Zhu",
      "year": "2000",
      "journal-title": "J. Neurochem."
    },
    {
      "key": "2023072509420834200_R59",
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      "DOI": "10.1097/00005792-198105000-00004",
      "article-title": "Immune complexes, complement, and anti-DNA in exacerbations of systemic lupus erythematosus",
      "volume": "60",
      "author": "Lloyd",
      "year": "1981",
      "journal-title": "Medicine."
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    {
      "key": "2023072509420834200_R60",
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      "article-title": "Serum amyloid-A concentration in inflammatory diseases and its relationship to the incidence of reactive systemic amyloidosis",
      "volume": "2",
      "author": "De Beer",
      "year": "1982",
      "journal-title": "Lancet."
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      "key": "2023072509420834200_R61",
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      "DOI": "10.1016/S0171-2985(98)80032-6",
      "article-title": "C1q deficiencies and C1q in autoimmunity",
      "volume": "199",
      "author": "Walport",
      "year": "1998",
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