Function of the Lectin Domain of Mac-1/Complement Receptor Type 3 (CD11b/CD18) in Regulating Neutrophil Adhesion

Xia, Yu; Borland, Gita; Huang, Junhua; Mizukami, Ikuko F.; Petty, Howard R.; Todd, Robert F.; Ross, Gordon D.

doi:10.4049/jimmunol.169.11.6417

Cited by 74 publications

(50 citation statements)

References 59 publications

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“…The PI3K/cytohesin-1-mediated activation of CR3 we describe represents a novel and additional mechanism of CR3 activation to previously described functional associations between CR3 and several GPI-linked proteins, including, Fc␥RIIIB (57), CD87 (58), and CD14 by itself (59). Such receptor clustering appears to occur in a dynamic microenvironment provided at the cell surface by lipid raft microdomains, which facilitate ligand-specific cellular responses initiated by GPI-linked molecules (60).…”

Section: Discussionsupporting

confidence: 56%

Cross-Talk between CD14 and Complement Receptor 3 Promotes Phagocytosis of Mycobacteria: Regulation by Phosphatidylinositol 3-Kinase and Cytohesin-1

Sendide

Reiner

Lee

et al. 2005

The Journal of Immunology

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The glycosylphosphatidyl anchored molecule CD14 to the monocyte membrane plays a prominent role in innate immunity, and the paradigms for CD14 selective signaling are beginning to be elucidated. In this study, transfected human monocytic cell line THP-1 and Chinese hamster ovary (CHO) fibroblastic cells were used to examine phagocytosis of Mycobacterium bovis bacillus Calmette-Guérin (BCG). Flow cytometry was combined with molecular and biochemical approaches to demonstrate a dual mechanism for BCG internalization involving either CD14 alone or a CD14-regulated complement receptor (CR)3-dependent pathway. Phagocytosis by CD14-positive THP-1 cells was attenuated by phosphatidylinositol-3 inhibitors LY294002 and wortmannin and experiments using transfected CHO cells showed substantial accumulation of phosphatidylinositol-3,4,5-trisphosphate at the BCG attachment site in CHO cells expressing CD14 and TLR2 suggesting that bacteria bind to CD14 and use TLR2 to initiate a PI3K signaling pathway. Additional experiments using blocking Abs showed that anti-TLR2 Abs inhibit phagocytosis of BCG by THP-1 cells. Furthermore, knockdown of cytohesin-1, a PI3K-regulated adaptor molecule for β2 integrin activation, specifically abrogated CD14-regulated CR3 ingestion of BCG consistent with the observation of physical association between CR3 and cytohesin-1 in cells stimulated with mycobacterial surface components. These findings reveal that mycobacteria promote their uptake through a process of “inside-out” signaling involving CD14, TLR2, PI3K, and cytohesin-1. This converts low avidity CR3 into an active receptor leading to increased bacterial internalization.

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Section: Discussionsupporting

confidence: 56%

Cross-Talk between CD14 and Complement Receptor 3 Promotes Phagocytosis of Mycobacteria: Regulation by Phosphatidylinositol 3-Kinase and Cytohesin-1

Sendide

Reiner

Lee

et al. 2005

The Journal of Immunology

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“…This finding is in line with previous evidence that (1) the migration of PNH neutrophils across endothelium is significantly impaired, 61 and (2) the acquisition of the active conformation of the CD11b/CD18 complex is significantly reduced by treatment with phosphatidylinositol-specific phospholipase C, which removes approximately 70% of cell surface GPI-anchored proteins. 62 It is likely that the absence of cross-talk between the CD11b/CD18 complex and selected GPI-anchored molecules is the reason why neutrophils from patients with PNH display functional defects. Thus, the blockage of CD157 through appropriate mAbs on normal neutrophils or the absence of CD157 (due to a somatic mutation) on PNH neutrophils has the same functional consequences.…”

Section: Discussionmentioning

confidence: 99%

CD157 is an important mediator of neutrophil adhesion and migration

Funaro¹,

Ortolan²,

Ferranti³

et al. 2004

Blood

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CD157, a glycosylphosphatidylinositol (GPI)-anchored protein encoded by a member of the CD38 NADase/ADP-ribosyl cyclase gene family, is expressed on the surface of most human circulating neutrophils. This work demonstrates that CD157 is a receptor that induces reorganization of the cytoskeleton and significant changes in cell shape, and that signals mediated by CD157 act through modulation of cytosolic Ca 2؉ concentration. These signals are independent of the products of CD157's enzymatic activities (ie, cyclic adenosine diphosphate [ADP]-ribose and ADP-ribose). Indeed, the enzymatic activities of CD157 in circulating neutrophils as well as in dimethyl sulfoxide (DMSO)-differentiated (CD157 ؉ / CD38 ؊ ) HL-60 cells, are hardly detectable. This work also shows that the receptorial activity relies on cross-talk between CD157 and ␤ 2 integrin. CD157 localizes in GM1-enriched lipid rafts and, upon activation, it migrates to the uropod, a structure specialized in motility and adhesive functions. Indeed, CD157 is involved in adhesion to extracellular matrix proteins and in chemotaxis induced in vitro by formylmethionyl-leucyl-phenylalanine (fMLP). These findings were consistent with the results obtained in neutrophils from patients with paroxysmal nocturnal hemoglobinuria (PNH), in which CD157 is deficient. These neutrophils showed constant defects in adhesion and migration. Our data attribute specific and crucial roles to CD157 in the regulation of innate immunity during inflammation. IntroductionHuman CD157 is a glycosylphosphatidylinositol (GPI)-linked glycoprotein encoded by a member of the NADase/adenosine diphosphate (ADP)-ribosyl cyclase gene family, which also includes CD38. 1 The CD157 and CD38 molecules are pleiotropic in function, acting both as ectoenzymes and receptors. [2][3][4] CD157 is abundantly expressed by myeloid lineage from precursors to differentiated stages 5 by bone marrow stromal cells, synovial cells, endothelial cells, and other cell types. 6 Functional analysis by means of agonistic monoclonal antibodies (mAbs) mimicking natural ligand(s) suggested that CD157 could act as a receptor with signal transduction capacity. However, as CD157 lacks a cytoplasmic domain, it must associate with some "conventional" receptor(s) to transduce signals; much in the same way as CD38, which has a short intracellular domain, CD157 acts as a parasite on specific receptors to compensate for its structural ineptitude to exert receptorial functions. 7,8 In concert with monocytes and tissue macrophages, neutrophils carry out many of the major functional responses of the innate immune system. They participate in inflammatory responses, such as host resistance to infection, and in detrimental host inflammatory reactions, including arthritis, septic shock, stroke, and transplantation rejection. The regulation of neutrophil recruitment into the inflammatory sites and neutrophil clearance are critical processes assuring effective host defense without tissue injury. Neutrophil extravasation is a multistep process depe...

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“…Indeed, it is well-established that CR3 functions require accessory signals, including that provided by ␣ v ␤ 3 integrin (5, 31). In addition, CR3 is able to form membrane complexes with some other receptors (32,33), which are necessary for its activity.…”

Section: Discussionmentioning

confidence: 99%

Coxiella burnetii Avoids Macrophage Phagocytosis by Interfering with Spatial Distribution of Complement Receptor 3

Capo

Moynault

Collette

et al. 2003

The Journal of Immunology

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Phagocytosis is a highly localized event requiring the formation of spatially and temporally restricted signals. Numerous microorganisms have taken advantage of this property to invade host cells. Coxiella burnetii, the agent of Q fever, is an obligate intracellular bacterium that has developed a survival strategy in macrophages based on subversion of receptor-mediated phagocytosis. The uptake of C. burnetii is mediated by αvβ3 integrin and is restricted by impaired cross-talk of αvβ3 integrin and complement receptor 3 (CR3) (CD11b/CD18). In this study, we showed that CR3 molecules remained outside the pseudopodal extensions induced by C. burnetii in THP-1 monocytes, although αvβ3 integrin was present in the pseudopods. Chemoattractants such as RANTES restored CR3 localization to the front of pseudopodal extensions and increased C. burnetii phagocytosis, demonstrating that the localization of CR3 is critical for bacterial uptake. In addition, monocyte activation due to the expression of HIV-1 Nef protein also restored CR3-mediated phagocytosis of C. burnetii by allowing CR3 redistribution toward bacterial-induced pseudopods. The redistribution of CR3 and increased C. burnetii phagocytosis in THP-1 cells stimulated by RANTES or expressing Nef were associated with the inhibition of intracellular replication of C. burnetii. Hence, the localization of CR3 is critical for bacterial phagocytosis and also for the control of bacterial replication. This study describes a nonpreviously reported strategy of phagocytosis subversion by intracellular pathogens based on altered localization of monocyte receptors.

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Function of the Lectin Domain of Mac-1/Complement Receptor Type 3 (CD11b/CD18) in Regulating Neutrophil Adhesion

Cited by 74 publications

References 59 publications

Cross-Talk between CD14 and Complement Receptor 3 Promotes Phagocytosis of Mycobacteria: Regulation by Phosphatidylinositol 3-Kinase and Cytohesin-1

Cross-Talk between CD14 and Complement Receptor 3 Promotes Phagocytosis of Mycobacteria: Regulation by Phosphatidylinositol 3-Kinase and Cytohesin-1

CD157 is an important mediator of neutrophil adhesion and migration

Coxiella burnetii Avoids Macrophage Phagocytosis by Interfering with Spatial Distribution of Complement Receptor 3

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