Critical role of Kupffer cell CR3 (CD11b/CD18) in the clearance of IgM-opsonized erythrocytes or soluble β-glucan

Yan, Jun; Větvička, Václav; Xia, Yu; Hanikýřová, M.; Mayadas, Tanya N.; Ross, Gordon D.

doi:10.1016/s0162-3109(99)00157-5

Cited by 60 publications

(44 citation statements)

References 60 publications

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“…Our in vitro studies suggest that complement activation and C3b deposition can suppress the inhibitory action of IgG, possibly by modulating interaction between the opsonized cells and Fc␥RI. Alternatively, the C3 fragments deposited on the RTXopsonized substrate cells may provide ligands such as iC3b which can engage CR3 on effector cells (35), thus enhancing cell-cell FIGURE 6. Single-color immunohistochemistry analyses of frozen sections from the s.c. model also revealed shaving of CD20.…”

Section: Discussionmentioning

confidence: 99%

Rituximab-CD20 Complexes Are Shaved from Z138 Mantle Cell Lymphoma Cells in Intravenous and Subcutaneous SCID Mouse Models

Williams²,

Cousar

et al. 2007

The Journal of Immunology

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Infusion of standard-dose rituximab (RTX) in chronic lymphocytic leukemia (CLL) patients promotes rapid complement activation and deposition of C3 fragments on CLL B cells. However, immediately after RTX infusions, there is substantial loss (shaving) of CD20 from circulating malignant cells. Because shaving can compromise efficacies of anticancer immunotherapeutic mAbs, we investigated whether shaving occurs in SCID mouse models. Z138 cells, a B cell line derived from human mantle cell lymphoma, were infused i.v. or s.c. The i.v. model recapitulates findings we previously reported for therapeutic RTX in CLL: i.v. infused RTX rapidly binds to Z138 cells in lungs, and binding is accompanied by deposition of C3 fragments. However, within 1 h targeted cells lose bound RTX and CD20, and these shaved cells are still demonstrable 40 h after RTX infusion. Z138 cells grow in tumors at s.c. injection sites, and infusion of large amounts of RTX (0.50 mg on each of 4 days) leads to considerable loss of CD20 from these cells. Human i.v. Ig blocked shaving, suggesting that FcγRI on cells of the mononuclear phagocytic system promote shaving. Examination of frozen tumor sections from treated mice by immunofluorescence revealed large areas of B cells devoid of CD20, with CD20 intact in adjacent areas; it is likely that RTX had opsonized Z138 cells closest to capillaries, and these cells were shaved by monocyte/macrophages. The shaving reaction occurs in neoplastic B cells in tissue and in peripheral blood, and strategies to enhance therapeutic targeting and block shaving are under development.

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Section: Discussionmentioning

confidence: 99%

Rituximab-CD20 Complexes Are Shaved from Z138 Mantle Cell Lymphoma Cells in Intravenous and Subcutaneous SCID Mouse Models

Williams²,

Cousar

et al. 2007

The Journal of Immunology

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“…The IgM mAb-C3b substrate contains no IgG Fc, and little transfer of this substrate was observed; however, this substrate induced significant E phagocytosis. Yan et al (15) have indeed demonstrated in mice that, via CR3, macrophages promote clearance of IgMopsonized E containing deposited C3b and iC3b. An understanding of the determining factors in the decision between phagocytosis vs transfer could have implications in future therapeutic approaches for immune-mediated anemias.…”

Section: Transfer Vs Phagocytosismentioning

confidence: 96%

Processing of C3b-Opsonized Immune Complexes Bound to Non-Complement Receptor 1 (CR1) Sites on Red Cells: Phagocytosis, Transfer, and Associations with CR1

Craig

Waitumbi

Taylor

2005

The Journal of Immunology

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Severe anemia is a lethal complication of Plasmodium falciparum malaria, particularly in children. Recent studies in children with severe P. falciparum anemia have demonstrated elevated levels of E-bound Abs, reduced E-associated complement receptor 1 (CR1) and decay-accelerating factor (DAF), and pronounced splenic enlargement, suggesting a mechanism for E loss involving Abs, complement, and phagocytosis. Motivated by these reports, we have developed an in vitro model in which human E with Abs and complement bound to CR1, DAF, or glycophorin A are incubated with model human macrophages (the THP-1 cell line). Previous work has demonstrated that immune complex (IC) substrates bound to E CR1, either by an Ab or via C3b, are transferred to macrophages with loss of CR1. In this study, we report that IC bound to DAF or glycophorin A by an Ab linkage are also transferred to macrophages. DAF is lost from the E during the transfer of DAF-bound IC, but the transfer of CR1-bound IC does not lead to a significant loss of DAF. Using glycophorin A-bound IC, we observe competition between transfer of IC and phagocytosis of the E: a fraction (≤15%) of the E was phagocytosed, while the remaining E were stripped of IC. We also examined the organization of CR1 and DAF in the presence of E-bound Ab/complement. We find that CR1, but not DAF, colocalizes with IgM mAb-C3b and IC-C3b substrates attached to glycophorin A. We observe that the binding of the IgM mAb-C3b to glycophorin A induces a novel unclustering of CR1.

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“…Macrophages express at least one Fc receptor that can recognize IgM, the Fc␣/ receptor (46). However IgM also powerfully activates complement, and in vivo studies actually show that the KC uptake of IgMopsonized erythrocytes is mediated in large part by the complement receptor CR3, as demonstrated with CR3 KO mice (64). In addition, it has recently been discovered that KCs express CRIg, a C3b receptor that is important for the clearance of opsonized bacteria from the circulation (20).…”

Section: Vol 82 2008 Mechanisms For Uptake Of Adenovirus By Kupffermentioning

confidence: 99%

Clearance of Adenovirus by Kupffer Cells Is Mediated by Scavenger Receptors, Natural Antibodies, and Complement

Tian

Smith

et al. 2008

J Virol

172

223

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In the current study, we systematically quantified the contributions of various receptors and plasma proteins to the clearance of Ad by KCs. We found that scavenger receptors are a predominant mechanism for the clearance of Ad by KCs. In addition, we found that Ad is opsonized by natural immunoglobulin M antibodies and complement and that these opsonins play a contributory role in the clearance of Ad by KCs. We also examined additional mechanisms that have been postulated to be involved in the clearance of Ad, including the binding of Ad to platelets and vitamin K-dependent coagulation factors, but we found that neither of these were required for the clearance of Ad by KCs.

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Critical role of Kupffer cell CR3 (CD11b/CD18) in the clearance of IgM-opsonized erythrocytes or soluble β-glucan

Cited by 60 publications

References 60 publications

Rituximab-CD20 Complexes Are Shaved from Z138 Mantle Cell Lymphoma Cells in Intravenous and Subcutaneous SCID Mouse Models

Rituximab-CD20 Complexes Are Shaved from Z138 Mantle Cell Lymphoma Cells in Intravenous and Subcutaneous SCID Mouse Models

Processing of C3b-Opsonized Immune Complexes Bound to Non-Complement Receptor 1 (CR1) Sites on Red Cells: Phagocytosis, Transfer, and Associations with CR1

Clearance of Adenovirus by Kupffer Cells Is Mediated by Scavenger Receptors, Natural Antibodies, and Complement

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