The major Fc receptor in blood has a phosphatidylinositol anchor and is deficient in paroxysmal nocturnal haemoglobinuria

Selvaraj, Periasamy; Rosse, Wendall F.; Silber, Robert; Springer, Timothy A.

doi:10.1038/333565a0

Cited by 363 publications

(164 citation statements)

References 25 publications

Supporting

Mentioning

152

Contrasting

Unclassified

Order By: Relevance

“…This protein is also a Pltailed protein like the Fc?'RIII. The lowered expression of these two Pldinked proteins in CML seems to follow the trend that is observed with respect to the decreased expression of Pl-linked proteins, leukocyte alkaline phosphatase, acetylcholine esterase, FcyRIII and dccay acceleration factor in PNH patients [13][14][15][16]. In the latter disorder however, the lowered expression of these proteins is believed to be associ~te£ -,,.…”

Section: Northern Hloltingmentioning

confidence: 72%

Decreased expression of FcγRIII mRNA in leukemic granulocytes

Monteiro¹,

Advani

Gothoskar³

et al. 1992

FEBS Letters

View full text Add to dashboard Cite

Morphologically mature granulocytes from patients with chronic myeloid leukemia show significant impairment in their ability to internalize aggregated IgG, a ligand that is rapidly phagocytosed by normal human granulocytes. With a view to understand the molecular basis of this defect, normal and leukemic granulocytes were examined for the steady-state levels ofmRNA for Fc?'RIIL a memb=are-associat~xl receptur that initially binds and traps the !gG-opsonized antigens. Northern blot analyses revealed that the level ofthe specific mRNA in CP,[L granulocytes was between 0.08 and 0.69 times that seen in the normal granulocytes. This could be one of the contributory factors for the observed endocytic defect in the leukemic granulocytes.

show abstract

Section: Northern Hloltingmentioning

confidence: 72%

Decreased expression of FcγRIII mRNA in leukemic granulocytes

Monteiro¹,

Advani

Gothoskar³

et al. 1992

FEBS Letters

View full text Add to dashboard Cite

show abstract

“…The anti-CD16 nonblocking monoclonal antibody (mAb) 214.1 (murine IgG1) was a generous gift from Dr. Howard Fleit (State University of New York, Long Island). The anti-CD16 adhesion blockade mAb CLBFcgran-1 (murine IgG2a) was purified in house from hybridomas as previously described (20). Cleavage of CLBFcgran-1 into Fab fragments was done by Lampire (Pipersville, PA).…”

Section: Methodsmentioning

confidence: 99%

Affinity and Kinetic Analysis of Fcγ Receptor IIIa (CD16a) Binding to IgG Ligands

Jiang²,

Nagarajan

et al. 2007

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Binding of pathogen-bound immunoglobulin G (IgGFc ␥ receptors (Fc␥Rs) 7 are a family of cell surface glycoproteins with varying affinities for the Fc region of immunoglobulins G (IgG). Three classes of human Fc␥Rs have been described: Fc␥RI (CD64), Fc␥RII (CD32), and Fc␥RIII (CD16), which are widely distributed in hematopoietic cell lineages. These include at least 12 different isoforms many of which are polymorphic. For example, CD16 has two isoforms, a and b, that differ by six amino acids in the extracellular domain and the presence (CD16a) or absence (CD16b) of the transmembrane and cytoplasmic domains (1).The IgG-Fc␥R interaction-mediated binding of antibody-opsonized pathogens to leukocytes is a key event by which antibody effector functions are initiated. Kinetic rates and binding affinity are critical determinants of an IgG-Fc␥R interaction, as they control how likely and how rapidly such binding will occur, how many bonds will be formed, and how long the bonds last. In addition, it has been hypothesized that these parameters are related to the signaling events following the initial binding (2-4). Using a micropipette method, we have measured the kinetic rates and binding affinities of several IgG-Fc␥R interactions when both interacting molecules are anchored on apposing surfaces. We found that in this assay the half-lives of these IgG-Fc␥R bonds are in the order of seconds (5-9).In addition to interaction parameters of surface-linked molecules, the kinetic rates and affinities of Fc␥Rs for soluble IgG are also of interest, because in vivo interactions of immobilized IgG to leukocyte Fc␥Rs are subject to competitive binding of soluble antibodies in sera. Of the three Fc␥Rs, CD64 binds to monomeric IgG with high affinity (K d ϳ tens of nM) (10), CD32 and CD16b are of low affinities (K d , several and several tens of M, respectively) (6, 11, 12), and CD16a is considered as an intermediate affinity receptor (K d ϳ hundreds of M) for monomeric IgG (6,10,12). In addition to the above results, which were obtained by conventional assays using Fc␥R-expressing cells, there were two studies using the surface plasmon resonance (SPR) technology and soluble Fc␥Rs. Galon et al. (13) reported half-lives of the order of 10 min and equilibrium dissociation constants of several micromolar for sCD16b NA2 binding to human (h) IgG1 and IgG3. By comparison, Maenaka et al. (14) found a much faster off-rate (half-lives of the order of seconds) but similar K d for IgG-sCD16b NA2 binding. Here, we report kinetic and affinity measurements of a soluble dimeric human Fc␥RIIIa (sCD16a) interacting with various IgG ligands in both monomeric and multimeric forms using SPR. We found that sCD16a interacted with monomeric rabbit (Rb) IgG, hIgG, hIgG1, and hIgG3 with on-rates of 1.8 ϫ 10 4 , 6.5 ϫ 10 3 , 8.2 ϫ 10 3 , and 1.1 ϫ 10 4 M Ϫ1 s Ϫ1, off-rates of 1.9 ϫ 10 Ϫ2 , 4.7 ϫ 10 Ϫ3 , 5.7 ϫ 10 Ϫ3 , and 5.9 ϫ 10 Ϫ3 s Ϫ1 , and equilibrium dissociation constants of 1.1, 0.72, 0.71, and 0.56 M, respectively. sCD16a bound with aggregated li...

show abstract

“…However, relatively little is known about the induction and the mechanism(s) of such processes. Although Fc␥RIIIb is GPI anchored to the cell membrane (18), several groups have established surprisingly that it can transduce signals by itself (19 -21). In contrast, others have stated that Fc␥RIIIb must cooperate with one or several neighboring transmembrane partners.…”

mentioning

confidence: 99%

Cross-Linking of Human FcγRIIIb Induces the Production of Granulocyte Colony-Stimulating Factor and Granulocyte-Macrophage Colony-Stimulating Factor by Polymorphonuclear Neutrophils

Durand¹,

Renaudineau²,

Pers³

et al. 2001

The Journal of Immunology

View full text Add to dashboard Cite

We have reported that human autoantibodies reacting with the polymorphonuclear neutrophil (PMN)-anchored FcγRIIIb (CD16) protect these cells from spontaneous apoptosis. In this study, we used anti-CD16 F(ab′)2 to delineate the mechanism(s) whereby the PMN life span is extended. As documented using four methods, CD16 cross-linking impeded spontaneous apoptosis, whereas anti-CD18 F(ab′)2 exerted no effect. Incubation of PMNs with anti-CD16 prevented the up-regulation of β2 integrins, particularly CD11b, which is the α-chain of complement receptor type 3, but also CD18, which is its β-chain, as well as CD11a and CD11c. Anti-CD16-conditioned supernatant of PMNs diminished the percentage of annexin V-binding fresh PMNs after another 18 h in culture, whereas the negative control anti-CD18 had no effect. The expression of mRNA for G-CSF and GM-CSF was induced by anti-CD16, followed by the release of G-CSF and GM-CSF in a dose-dependent manner. Anti-G-CSF and anti-GM-CSF mAbs abrogated the antiapoptotic effect of the related growth factors. The delay in apoptosis was accompanied by a down-regulated expression of Bax, and a partial reduction of caspase-3 activity. These data suggest an autocrine involvement of anti-CD16-induced survival factors in the rescue of PMNs from spontaneous apoptosis. Thus, apoptosis of aged PMNs can be modulated by signaling through FcγRIIIb, which may occur in patients with PMN-binding anti-FcγRIIIb autoantibodies.

show abstract

The major Fc receptor in blood has a phosphatidylinositol anchor and is deficient in paroxysmal nocturnal haemoglobinuria

Cited by 363 publications

References 25 publications

Decreased expression of FcγRIII mRNA in leukemic granulocytes

Decreased expression of FcγRIII mRNA in leukemic granulocytes

Affinity and Kinetic Analysis of Fcγ Receptor IIIa (CD16a) Binding to IgG Ligands

Cross-Linking of Human FcγRIIIb Induces the Production of Granulocyte Colony-Stimulating Factor and Granulocyte-Macrophage Colony-Stimulating Factor by Polymorphonuclear Neutrophils

Contact Info

Product

Resources

About