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Blood, Vol. 95 No. 9 (May 1), 2000:
pp. 2943-2946
PHAGOCYTES
Wiskott-Aldrich syndrome protein is necessary for efficient
IgG-mediated phagocytosis
Roberto Lorenzi,
Paul M. Brickell,
David R. Katz,
Christine Kinnon, and
Adrian J. Thrasher
Department of Molecular Immunology and Department of Molecular
Haematology, Institute of Child Health, London, England; Department of
Immunology, University College London Medical School, London, England.
 |
Abstract |
Interactions between the Wiskott-Aldrich (WAS) protein (WASp), small
GTPases, and the cytoskeletal organizing complex Arp2/3 appear to be
critical for the transduction of signals from the cell membrane to the
actin cytoskeleton in hematopoietic cells. This study shows that
Fc -receptor (FcR)-mediated phagocytosis is impaired in
WASp-deficient peripheral blood monocytes, and that in macrophages,
formation of the actin cup and local recruitment of tyrosine
phosphorylated proteins is markedly attenuated. Results also show that,
in normal macrophages, WASp itself is actively recruited to the cup,
suggesting that assembly of this specialized cytoskeletal structure is
dependent on its expression.
(Blood. 2000;95:2943-2946)
© 2000 by The American Society of Hematology.
| |
Introduction |
The Wiskott-Aldrich syndrome (WAS) protein (WASp) is a member of a
family of cytoplasmic proteins that share similar domain structures,
and that which are believed to be responsible for the transduction of
signals from the cell membrane to the actin cytoskeleton.1,2 Interactions between WASp, the Rho family GTPase CDC42,3,4 and the cytoskeletal organizing complex Arp2/35 appear to be critical to this function, which when
disturbed translates into measurable defects of cell polarization and
motility.6,7 Patients with WAS contain a mutant copy of the
WAS gene and in most cases there is no detectable expression of
WASp in primary hematopoietic cells.8 Apart from studies
that have demonstrated negative effects following injection of an
isolated WASp CDC42-Rac interactive binding (CRIB) domain9
into J774 mouse macrophages, the role of WASp in FcR-mediated
phagocytosis and linked signaling pathways is undefined.
| |
Materials and methods |
Patient samples
All patients with WAS exhibited a severe clinical phenotype, and
none expressed detectable WASp in mononuclear cell lysates by Western
blotting with rabbit polyclonal antisera SK3 as previously described
(raised against C-terminal amino acids 487-501).8 Patient
W-BL contains a G insertion at position 1357 in exon 10, resulting in a
frameshift. Patient W-SS contains a T to C substitution that disrupts
the splice donor site in intron 9. Patients W-JG and W-SG are siblings
with an identical T to C missense mutation at nucleotide 284 in exon 2 (patients 3 and 4 in reference 8).
Purification of PBMC and phagocytosis assay
The PBMC were isolated by Histopaque-1077 (Sigma, Poole, England)
gradient centrifugation and 2-5 × 105 cells were
incubated at 37°C for various lengths of time with 15 to 20 mL
fluorescein isothiocyanate (FITC)- Escherichia
coli (Phagotest, Orpegen Pharma, Heidelberg, Germany), preopsonized with human IgG (Pierce). After incubation, cells were quenched, washed,
and then stained with PE-CD14 monoclonal antibody (mAb) (Dako, Ely,
England). FACS analysis (> 50 000 events acquired) was performed on
a FacscaliburII (Beckton-Dickinson) by gating the monocytic fraction by
forward and side scatter and analyzing the FL1 and FL2 channels by
dotplot at each time point. The percentage of phagocytosis was
calculated after gating the CD14 and fluorescein isothiocyanate (FITC)
double positive events against a negative control sample incubated at
0°C. Experiments were performed in duplicate or triplicate, with
normal control and WAS samples processed in parallel. Statistical
analysis consisted of a 2-tail Student t test adjusted for
unequal variances: ** = P < 0.002, * = P < 0.05, n = 3.
Primary macrophage cultures and adherent phagocytosis assay
The PBMC (5 × 105 cells) were seeded on to
microchamber slides (Nunc, Rochester, NY) and nonadherent cells were
then induced to differentiate into macrophages by incubation in
Macrophage-SFM medium (Gibco-BRL, Paisley, Scotland) supplemented with
recombinant human macrophage colony-stimulating factor (M-CSF, R&D
System, Abingdon, England), as previously described.7 Latex
beads (3µm diameter; Sigma) were incubated with 2% (w/v) bovine
serum albumin (BSA) overnight at room temperature and opsonized by
incubating with 1:200 dilution of rabbit anti-BSA IgG (Sigma) for 2 hours at 37°C. Beads were then washed and resuspended in serum-free RPMI medium. Opsonization was checked with FITC-conjugated antirabbit IgG. Cells were starved of serum in M-CSF-free RPMI medium for 2 hours
before addition of IgG-opsonized latex beads at a ratio of 10 to 50 beads per cell. Beads were allowed to adhere to cells for 15 minutes on
ice in cold RPMI medium. Unbound beads were washed off, and cells
incubated for a further 15 minutes at 37°C in prewarmed medium.
Phagocytosis was stopped by fixation in 4% (w/v) paraformaldehyde for
10 minutes, followed by quenching in 100 mmol/L ammonium acetate for 5 minutes. Cells were permeabilized by incubating for 4 minutes in 0.1%
(v/v) Triton- × 100, followed by blocking with excess human IgG
(Pierce, Chester, England). F-actin was visualized by incubation with
rhodamine-labeled phalloidin (Molecular Probes, Leiden, Netherlands).
Tyrosine-phosphorylated proteins were detected with mAb PY20
(FITC-PY20; Santa Cruz, Santa Cruz, CA) followed by FITC-conjugated
sheep antimouse IgG (Boehringer Mannheim, Indianapolis, IN). Slides
were mounted in Citifluor containing 10 nmol/L DAPI, and images
recorded with a Nu200 CCD camera (Photometrics, Waterloo, ON) driven by
IPLab Spectrum software (Signal Analytics, Vienna, VA). Images were
handled with Adobe Photoshop.
Plasmid constructs and cell transfection
Plasmid vector pEGFP-WASp was constructed by amplifying the human
WASp coding region by polymerase chain reaction and cloning it into
pEGFP-C2 (Clontech, Basingstone, England), in frame and downstream of
the EGFP coding region. Cos7 cells were transfected with Superfect
(Quiagen, Crawley, England). Primary human macrophages were transfected
with plasmid vector pEGFP-WASp by adenovirus-enhanced uptake14 with peptide 6.15
| |
Results and discussion |
To address this issue, we first assessed whether a measurable defect
in the efficiency of FcR-mediated phagocytosis could be detected in
primary PBMC peripheral blood monocytes from 4 WAS patients (null
mutants) (Figure 1). Freshly isolated
mononuclear cells were incubated with fluorescein-conjugated
Escherichia coli preopsonized with human IgG.
After cytofluorimetric analysis we measured the uptake in the
CD14+ monocyte-gated fraction and found an approximately
2-fold reduction in the efficiency of phagocytosis in all WAS patients
(Figure 1A). The difference between normal and WAS cells was most
pronounced at early time points, although the defect was not fully
restored even after 60 minutes, at which time the uptake in WAS cells
was still only 70% of normal (Figure 1B). The attenuation of
phagocytosis was also observed when measured at a single early time
point for different bacteria to cell ratios (Figure 1C). These findings suggest that there is a defect in the early events of FcR-mediated uptake that is intrinsic to WAS peripheral blood-derived monocytes.
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| Fig 1.
Phagocytosis mediated by Fc-R. (A) Time
course of phagocytosis of IgG-coated, FITC-labeled E coli by
CD14-positive peripheral blood monocytes (PBM) isolated from 4 WAS
patients (W-BL, W-SS, W-JG, W-SG; open bars) or from normal controls
(filled bars). (B) Efficiency of phagocytosis by WAS PBM compared to
normal control PBM. Pooled values from the 4 WAS patients are expressed
as a percentage of pooled values from the normal controls. (C)
Phagocytosis by normal (filled bars) and WAS (open bars) PBM, 15 minutes after addition of different amounts of IgG-coated, FITC-labeled
E coli. WAS PBM were from patient W-SS. Cell type specificity
of internalization was confirmed by demonstrating a negligible rate of
uptake of IgG-coated, FITC-labeled E coli by the
CD14 lymphocyte population (data not shown).
Treatment of PBM with 10 mmol/L cytochalasin D for 30 minutes abrogated
uptake of IgG-coated, FITC-labeled E coli to background levels
(data not shown).
|
|
FcR-mediated internalization requires polymerization of actin at the
site of ingestion and transient formation of an actin-rich phagocytic
cup that is shed shortly after internalization is
completed.10 Because the efficiency of FcR-mediated
phagocytosis in WAS monocytes appears to be most compromised at early
time points, we analyzed cup formation at these times following
incubation of adherent primary macrophages with IgG-coated latex beads.
In normal macrophages, FcR-mediated internalization was associated
with a broad rim of actin polymerization around the engulfed particles
(Figure 2A-C and D-F). For more than 80%
of cell-associated beads, the F-actin could also be shown to
co-localize with tyrosine phosphorylated proteins, reflecting assembly
of the active cytoskeletal complex (Figure 2C and F). In the residual
fraction, staining for F-actin or protein tyrosine phosphorylation was
variable, presumably reflecting heterogeneity in the maturation state
of the phagosome (data not shown).
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| Fig 2.
Defective formation of phagocytic cups in
WAS macrophages and recruitment of WASp during IgG-mediated
phagocytosis. (A-C and D-F) Two examples of phagocytic cup
formation in normal macrophages incubated with IgG-coated latex beads
(arrowheads). Cells were stained with rhodamine-phalloidin to show the
distribution of F-actin (A and D, red) and FITC-PY20 to show tyrosine
phosphorylation (B and E, green). Merged images (C and F) show
co-localization (yellow) of the 2 signals. (G-I and J-L) Two examples
of phagocytic cup formation (arrowheads) in WAS macrophages showing
F-actin. (G and J, rhodamine phalloidin) and tyrosine phosphorylation
(H and K, FITC-PY20). Merged images are also shown (I and L). In
contrast to normal phagocytic cups, those of WAS macrophages are
deficient in F-actin, giving the appearance of black disks surrounded
by a less well-formed rim. Furthermore, there is no apparent
accumulation of tyrosine phosphorylated proteins in the region of the
phagocytic cup. (M and N) Expression of EGFP (M) and EGFP-WASp fusion
protein (N) in Cos7 cells transiently transfected with plasmid vectors
pEGFP-C2 and pEGFP-WASp, respectively. (O-U) Distribution of EGFP-WASp
and actin in transfected normal human macrophages. Primary human
macrophages transfected with plasmid vector pEGFP-WASp show accentuated
cortical staining and co-localization of EGFP-WASp with F-actin
(EGFP-rhodamine phalloidin merged image (O). (P-R and S-U) Two examples
of transfected macrophages incubated with IgG-coated latex beads are
shown. (P and S) EGFP-WASp fusion protein, visualized using a FITC
filter. (Q and T) Rhodamine-phalloidin staining of F-actin. (R and U)
The merged images and sites of co-localization of EGFP-WASp fusion
protein and F-actin (yellow). An untransfected cell is also shown
alongside a cell expressing EGFP-WASp (S-U). In cells containing
phagocytosed latex beads, EGFP-WASp and F-actin both accumulate around
the particles, although some remained co-localized with F actin-rich
cortical areas in these cells. The scale bar represent 5µm.
|
|
We next analyzed the formation of phagocytic cups in WAS mutant cells.
In the absence of phagocytic stimuli, WAS macrophages lacked podosomes
and were mostly devoid of filopodia.6,11 On addition of
opsonized particles, typically 70% or more of WAS macrophages bound 1 or more beads in independent experiments, suggesting that particle
attachment is normal. However, when compared to normal macrophages, the
intensity of signal from polymerized actin in the immediate proximity
of the engulfed particle was markedly reduced (Figure 2G and J). We
then examined the local recruitment of tyrosine phosphorylated
proteins. These proteins (including WASp) are associated with the
regulated assembly and dissolution of the cytoskeletal complex. By
contrast with normal cells, at time points well within the range of
normal persistence of F-actin cups (in normal macrophages this extended
beyond 30 minutes), the level of protein tyrosine phosphorylation
around the engulfed particles was also markedly reduced (Figure 2H and K). The defects of actin polymerization and tyrosine phosphorylation were consistently observed in independent experiments on cells derived
from 3 WAS patients. These findings indicate that the formation of an
actin cup and assembly of an active cytoskeletal complex at the site of
phagocytosis are dependent on the presence of a normally functional WASp.
Finally, to determine whether WASp is actively recruited to the
phagocytic cup during this process, we constructed an expression vector
in which wild-type WASp is fused at the N-terminus to enhanced green
fluorescent protein (EGFP). When expressed in Cos7 cells, this fusion
protein exhibited expression patterns identical to those shown
previously for wild-type WASp, suggesting that the addition of EGFP
does not interfere with normal function (Figure 2N). In transfected
primary macrophages, where endogenous WASp is expressed, the EGFP-WASp
fusion protein was instead homogeneously distributed in the cytoplasm
in the absence of phagocytic stimuli, with areas of more pronounced
cortical staining that co-localized with F-actin (Figure 2O). On
addition of IgG-coated beads, the EGFP-fusion signal was mostly found
to relocate around the engulfed particle, and also co-localized with
F-actin (Figure 2P-R and S-U). These data indicate that WASp is
actively recruited into the phagocytic cup during FcR-mediated
phagocytosis in normal primary macrophages and may therefore play a
critical role in actin polymerization in situ during the early events
of particle uptake.
Recent studies have shown that FcR-mediated phagocytosis is at least
in part dependent on CDC42 and can be disturbed by overexpression of
the CRIB domain from WASp.9,12 Our findings are consistent with these because we have observed a decreased efficiency of FcR-mediated phagocytosis in WAS PBMC peripheral blood monocytes and
attenuation of localized actin polymerization during formation of the
phagocytic cup in differentiated WAS macrophages. In addition, we have
shown that EGFP-WASp fusion protein is actively relocated to the region
of the evolving cup. However, the phenotypic differences between WAS
mutant cells and those previously reported for rat basophilic leukemia
cells stably expressing dominant negative N17CDC42 are more
surprising.13 In these studies, expression of N17CDC42 was
permissive for the formation of actin-rich phagocytic cups, which
nevertheless failed to internalize the particles. In addition, the
accumulation of tyrosine phosphorylated proteins around the particle
was persistent. In marked contrast, our findings in primary human WAS
macrophages are of reduced phagosome-specific actin polymerization and
virtually absent tyrosine phosphorylation. The simplest interpretation
of these combined observations is that WASp itself is responsible for
recruitment of tyrosine phosphorylated proteins into the phagocytic
cup. In addition to being a final effector for CDC42, WASp may
therefore play a more central and proximal role in the assembly of a
regulated cytoskeletal complex consisting of Rho family proteins,
signaling molecules, and Arp2/3 complex at specialized sites of actin
polymerization. The multidomain structure of WASp and other family
members may well reflect this function. For the WAS itself, these
findings suggest that phagocytic defects may contribute significantly
to disease pathophysiology, both in terms of elimination of
microorganisms, and perhaps also the phagocytic uptake of apoptotic cells.
| |
Acknowledgments |
We thank Laura Machesky for critical reading of the manuscript and
the sharing of unpublished data, Robin May for valuable help in setting
up the phagocytosis assay, Steve Hart for the kind gift of transfection
peptides, Mike Blundell for construction of the EGFP-WASP fusion
construct, Gareth Jones for advice on macrophage primary cultures, and
Elaine O'Sullivan for critical reading of the manuscript.
| |
Footnotes |
Submitted November 10, 1999; accepted December 30, 1999.
Supported by grants from the Primary Immunodeficiency Association and
the National Lottery Charities Board.
A.J.T. is a Wellcome Trust senior clinical fellow.
Reprints: Roberto Lorenzi, Department of Molecular Immunology,
Institute of Child Health, 30 Guilford Street, London WC1N 1EH,
England; e-mail: r.lorenzi{at}ich.ucl.ac.uk.
The publication costs of this
article were defrayed in part by
page charge payment. Therefore,
and solely to indicate this fact,
this article is hereby marked
"advertisement"
in accordance with 18 U.S.C.
section 1734.
| |
References |
1.
Snapper SB, Rosen FS.
The Wiskott-Aldrich syndrome protein (WASP): roles in signaling and cytoskeletal organization.
Annu Rev Immunol.
1999;17:905-929[Medline]
[Order article via Infotrieve].
2.
Aspenstrom P, Lindberg U, Hall A.
Two GTPases, Cdc42 and Rac, bind directly to a protein implicated in the immunodeficiency disorder Wiskott-Aldrich syndrome.
Curr Biol.
1996;6:70-75[Medline]
[Order article via Infotrieve].
3.
Symons M, Derry JM, Karlak B, et al.
Wiskott-Aldrich syndrome protein, a novel effector for the GTPase CDC42Hs, is implicated in actin polymerization.
Cell.
1996;84:723-734[Medline]
[Order article via Infotrieve].
4.
Kolluri R, Tolias KF, Carpenter CL, Rosen FS, Kirchhausen T.
Direct interaction of the Wiskott-Aldrich syndrome protein with the GTPase Cdc42.
Proc Natl Acad Sci U S A.
1996;93:5615-5618[Abstract/Free Full Text].
5.
Machesky LM, Insall RH.
Scar1 and the related Wiskott-Aldrich syndrome protein, WASP, regulate the actin cytoskeleton through the Arp2/3 complex.
Curr Biol.
1998;8:1347-1356[Medline]
[Order article via Infotrieve].
6.
Binks M, Jones GE, Brickell PM, Kinnon C, Katz DR, Thrasher AJ.
Intrinsic dendritic cell abnormalities in Wiskott-Aldrich syndrome.
Eur J Immunol.
1998;28:3259-3267[Medline]
[Order article via Infotrieve].
7.
Zicha D, Allen WE, Brickell PM, et al.
Chemotaxis of macrophages is abolished in the Wiskott-Aldrich syndrome.
Br J Haematol.
1998;101:659-665[Medline]
[Order article via Infotrieve].
8.
MacCarthy-Morrogh L, Gaspar HB, Wang YC, et al.
Absence of expression of the Wiskott-Aldrich syndrome protein in peripheral blood cells of Wiskott-Aldrich syndrome patients.
Clin Immunol Immunopathol.
1998;88:22-27[Medline]
[Order article via Infotrieve].
9.
Caron E, Hall A.
Identification of two distinct mechanisms of phagocytosis controlled by different Rho GTPases.
Science.
1998;282:1717-1721[Abstract/Free Full Text].
10.
Harbottle RP, Cooper RG, Hart SL, et al.
An RGD-oligolysine peptide: a prototype construct for integrin-mediated gene delivery [see comments].
Hum Gene Ther.
1998;9:1037-1047[Medline]
[Order article via Infotrieve].
11.
Hart SL, Collins L, Gustafsson K, Fabre JW.
Integrin-mediated transfection with peptides containing arginine-glycine-aspartic acid domains.
Gene Ther.
1997;4:1225-1230[Medline]
[Order article via Infotrieve].
12.
Aderem A, Underhill DM.
Mechanisms of phagocytosis in macrophages.
Annu Rev Immunol.
1999;17:593-623[Medline]
[Order article via Infotrieve].
13.
Linder S, Nelson D, Weiss M, Aepfelbacher M.
Wiskott-Aldrich syndrome protein regulates podosomes in primary human macrophages.
Proc Natl Acad Sci U S A.
1999;96:9648-9653[Abstract/Free Full Text].
14.
Cox D, Chang P, Zhang Q, Reddy PG, Bokoch GM, Greenberg S.
Requirements for both Rac1 and Cdc42 in membrane ruffling and phagocytosis in leukocytes.
J Exp Med.
1997;186:1487-1494[Abstract/Free Full Text].
15.
Massol P, Montcourrier P, Guillemot JC, Chavrier P.
Fc receptor-mediated phagocytosis requires CDC42 and Rac1.
EMBO J.
1998;17:6219-6229[Medline]
[Order article via Infotrieve].
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|
G. O. C. Cory, R. Garg, R. Cramer, and A. J. Ridley
Phosphorylation of Tyrosine 291 Enhances the Ability of WASp to Stimulate Actin Polymerization and Filopodium Formation
J. Biol. Chem.,
November 15, 2002;
277(47):
45115 - 45121.
[Abstract]
[Full Text]
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H. Falet, K. M. Hoffmeister, R. Neujahr, and J. H. Hartwig
Normal Arp2/3 complex activation in platelets lacking WASp
Blood,
August 28, 2002;
100(6):
2113 - 2122.
[Abstract]
[Full Text]
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D. J. Seastone, E. Harris, L. A. Temesvari, J. E. Bear, C. L. Saxe, and J. Cardelli
The WASp-like protein Scar regulates macropinocytosis, phagocytosis and endosomal membrane flow in Dictyostelium
J. Cell Sci.,
March 9, 2002;
114(14):
2673 - 2683.
[Abstract]
[Full Text]
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J. C. Boldrick, A. A. Alizadeh, M. Diehn, S. Dudoit, C. L. Liu, C. E. Belcher, D. Botstein, L. M. Staudt, P. O. Brown, and D. A. Relman
Stereotyped and specific gene expression programs in human innate immune responses to bacteria
PNAS,
January 22, 2002;
99(2):
972 - 977.
[Abstract]
[Full Text]
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A. Oda, H. D. Ochs, L. A. Lasky, S. Spencer, K. Ozaki, M. Fujihara, M. Handa, K. Ikebuchi, and H. Ikeda
CrkL is an adapter for Wiskott-Aldrich syndrome protein and Syk
Blood,
May 1, 2001;
97(9):
2633 - 2639.
[Abstract]
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Y. Leverrier, R. Lorenzi, M. P. Blundell, P. Brickell, C. Kinnon, A. J. Ridley, and A. J. Thrasher
Cutting Edge: The Wiskott-Aldrich Syndrome Protein Is Required for Efficient Phagocytosis of Apoptotic Cells
J. Immunol.,
April 15, 2001;
166(8):
4831 - 4834.
[Abstract]
[Full Text]
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M. G. Coppolino, M. Krause, P. Hagendorff, D. A. Monner, W. Trimble, S. Grinstein, J. Wehland, and A. S. Sechi
Evidence for a molecular complex consisting of Fyb/SLAP, SLP-76, Nck, VASP and WASP that links the actin cytoskeleton to Fc{gamma} receptor signalling during phagocytosis
J. Cell Sci.,
January 12, 2001;
114(23):
4307 - 4318.
[Abstract]
[Full Text]
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R. May and L. Machesky
Phagocytosis and the actin cytoskeleton
J. Cell Sci.,
January 3, 2001;
114(6):
1061 - 1077.
[Abstract]
[PDF]
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Top
Abstract
Introduction