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HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Host defense role of platelets: engulfment of HIV and Staphylococcus aureus
occurs in a specific subcellular compartment and is enhanced by platelet activation
Tayebeh Youssefian, Arnaud Drouin, Jean-Marc Massé, Josette Guichard, and Elisabeth M. Cramer
Platelets can bind and phagocytose infectious microorganisms and so enable their
transport for a prolonged time. To investigate the subcellular events of these interactions, platelets were incubated either
with Staphylococcus aureus or with HIV
and analyzed by electron microscopy (EM)
and immuno-EM. HIV and bacteria internalization occurred exclusively within
platelets showing morphological evidence
of activation. Platelet activation enhanced
the degree of bacterial internalization.
Immunolabeling revealed that the engulfing vacuoles and the open canalicular
system (OCS) were composed of distinct
antigens. The engulfing vacuoles eventually became the site of prominent ␣-granule release. In platelets incubated with
HIV, characteristic endocytic vacuoles
were identified close to the plasma membrane, tightly surrounding 1 or 2 HIV
particles. Virus particles were also lo-
cated within the OCS. Immunogold labeling for the viral core protein p24 confirmed the presence of HIV within
platelets. Finally, examination of platelets
from a patient with acquired immunodeficiency syndrome and high viremia suggested that HIV endocytosis may also
occur in vivo. (Blood. 2002;99:4021-4029)
© 2002 by The American Society of Hematology
Introduction
Although the critical role of blood platelets in hemostasis and
thrombosis is clearly recognized, their capacity to function during
host defense against infection has received much less attention.
Thrombocytopenia is often a severe complication during or after
bacterial and viral infections. The mechanisms responsible appear
to be multiple: increased platelet destruction, due either to the
nonspecific deposition of circulating immune complexes on platelets or to the presence of specific antiplatelet antibodies, and
decreased platelet production.1,2 More specifically, several studies
have indicated that during infection with HIV, there is a direct
interaction of HIV with megakaryocytes and platelets: mature
megakaryocytic cells express CD4 along with HIV coreceptors
CXCR1, 2, and 4 and CCR3 and 5 on their surface3-6 and are thus
susceptible to HIV infection; productive infection of megakaryocytes by X4 and R5 HIV-1 isolates has also been shown7; and
megakaryocytes from seropositive subjects have been found to
contain viral RNA and antigens by in situ hybridization.3,8 These
are arguments for decreased platelet production. HIV-1 RNA has
also been detected in platelet preparations by reverse-transcriptase–
polymerase chain reaction, and platelets that are washed, but
depleted of leukocytes, appear to retain high concentration of
tightly associated HIV messenger RNA.9 A direct interaction
between platelets and HIV has also been shown.10 Moreover,
platelets also express the HIV coreceptors (CXCR1, 2, and 4 and
CCR 1, 3, and 4) on their surface.4,11
It is also conceivable that during bacterial infection, direct
interaction between platelets and bacteria may contribute to the
observed thrombocytopenia. Several studies performed in vitro on
the interaction of platelets with Staphylococcus aureus indicated
that the bacteria induce the platelet-release reaction and rapid
irreversible platelet aggregation in the presence of normal plasma;
in these experiments, internalization of S aureus by individual
platelets occasionally occurred.12-15 It has also been shown that
␣-toxin, the major cytolysin of S aureus, promotes blood coagulation by its attack on human platelets.16,17 Thus, infectious thrombocytopenias are secondary to multiple and combined mechanisms,
but each parameter deserves to be isolated and carefully studied
individually.
Therefore, the aim of this study was to use electron microscopy
(EM) and immuno-EM to fully elucidate the mechanism of direct
platelet-microorganism interactions, in particular those associated
with S aureus and HIV internalization by platelets. We also
examined the potential role of platelet activation on the ability of
platelets to internalize infectious microorganisms and documented
the subcellular distribution of platelet antigens during the interaction of platelets with bacteria. The interaction of platelets with HIV
was also investigated with specific immunogold labeling of internalized HIV, either in vitro or in vivo, within platelets of patients with
AIDS and thrombocytopenia.
From INSERM U 474, Institut Cochin, Paris, France, and Faculté de Médecine
Paris–Ile de France–Ouest, France.
Reprints: Elisabeth Cramer, INSERM U 474, Maternité 5ème étage, Hôpital de
Port-Royal, 123 Boulevard Port-Royal, 75014, Paris, France; e-mail: elisabeth.
[email protected].
Submitted December 6, 2001; accepted February 1, 2002. Prepublished online
as Blood First Edition Paper, April 30, 2002; DOI 10.1182/blood-2001-12-0191.
Supported by a fellowship from L’Association Nationale pour la Recherche
contre le SIDA (T.Y.).
BLOOD, 1 JUNE 2002 䡠 VOLUME 99, NUMBER 11
Materials and methods
Cells
Platelets were obtained from healthy donors by venipuncture into plastic
tubes containing EDTA or acid-citrate-dextrose (ACD)–C buffer. The
platelet-rich plasma was obtained by centrifugation for 15 minutes at 180g
and 22°C. Isolated platelets were obtained by centrifugation of platelet-rich
plasma for 5 minutes at 1100g and were washed 3 times with Tyrode buffer
(360 mM citric acid, 5 mM KCl, 2 mM CaCl2, 1 mM MgCl2, 103 mM
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.
© 2002 by The American Society of Hematology
4021
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BLOOD, 1 JUNE 2002 䡠 VOLUME 99, NUMBER 11
YOUSSEFIAN et al
glucose, pH 7.4) containing 0.35% bovine serum albumin (Sigma Chemical, St Louis, MO). Washed platelets were resuspended in Hanks balanced
salt solution (HBSS).
Platelets of a patient with AIDS, high plasma viremia, and thrombocytopenia were obtained by venipuncture into plastic tubes containing ACD-C,
fixed in whole blood in 1.5% glutaraldehyde for 1 hour, and washed 3 times
in 0.1 M phosphate buffer, pH 7.4.
Bacteria
Suspensions of S aureus were prepared from overnight broth cultures,
centrifuged for 5 minutes at 1500g, and washed 2 times with HBSS.
Bacteria were resuspended in HBSS and sonicated to disrupt
bacterial clusters.
Platelet-bacteria interaction
Washed platelets (2 ⫻ 109/mL) were incubated with S aureus suspension
with an excess of bacteria (1010/mL) at 37°C for 1 hour. The effect of
platelet activation was also studied by preactivating the platelets with 10
␮M adenosine 5⬘-diphosphate (ADP) for 30 minutes or 0.1 U/mL thrombin
for 5 minutes, with appropriate controls. Cells were then fixed by the
addition of glutaraldehyde up to a final concentration of 1% in 0.1 M
phosphate buffer.
Human immunodeficiency virus
The HIV-1 particles were obtained from the supernatant of peripheral blood
mononuclear cell (PBMC) culture of HIV-1–infected patients by centrifugation at 25 000g for 15 minutes and were resuspended in HBSS.
Platelet-HIV interaction
Washed platelets (2 ⫻ 109/mL) were directly incubated with a viral pellet
with reverse-transcriptase activity of approximately 10 000 cpm.
Antibodies
A pool of 3 monoclonal antibodies against the core protein p24 HIV-1 was a
generous gift from Dr H. R. Gelderblom (Berlin, Germany).18 Antihuman
polyclonal rabbit antibodies anti-␣IIb␤3,19 antiglycocalicin (anti–glycoprotein Ib [anti-GPIb]),20 and anti–P-selectin (CD62p)21 were kindly provided
by Dr Michael Berndt (Prahran, Victoria, Australia). Antifibrinogen22 was
purchased from Dako (Glostrup, Denmark). These antibodies were used at
10 ␮g/mL. Goat anti–rabbit and goat anti–mouse immunoglobulin-G
fractions coupled to 10 nm gold particles (GAR-G10, GAM-G10) were
purchased from British Biocell International (Cardiff, United Kingdom)
and used at 1/30 dilution.
Electron microscopy
Samples were fixed in 1.5% glutaraldehyde for 1 hour and washed 3 times
in 0.1 M phosphate buffer, pH 7.4. For morphologic examination, fixed
platelets were postfixed in 1% osmic acid, dehydrated in ethanol, and
embedded in Epon by standard methods.
Immunolabeling
For immunolabeling experiments, fixed platelets were embedded in sucrose
(for cryosections)23 or glycolmethacrylate (for ultrathin sections), and the
immunochemical reactions were performed on thin sections collected on
nickel grids.24 Briefly, we labeled sections first by incubating them with the
primary antibodies for 2 hours at 22°C in a humidified atmosphere and then
washing them thoroughly in Tris-buffered saline. This was followed by
incubation with GAR-G10 or GAM-G10 for 1 hour at 22°C. Samples were
counterstained and were observed on a Philips CM 10 electron microscope
(Eindhoven, The Netherlands).
Results
Platelet and bacteria interaction
Activated platelets are able to internalize bacteria (S aureus).
The ultrastructural examination of washed platelets incubated with
S aureus demonstrated that the internalization of bacteria within
platelets was rare. Nevertheless, in the few platelets where bacteria
internalization appeared to have occurred, the platelets presented
morphological signs of activation with characteristic spherical
shape, bristled surface with a few pseudopods, dilation of the open
canalicular system (OCS), and rare cytoplasmic granules.
Platelet activation increases bacteria internalization. To elucidate whether platelet activation preceded and facilitated bacteria
internalization or whether bacteria uptake induced platelet activation, washed platelets were activated by ADP or thrombin and
incubated with bacteria. Examination of platelet samples incubated
with S aureus in the absence of an exogenous platelet activator
demonstrated that platelets remained discoid and apparently inactivated, and bacteria were retrieved in the vicinity of platelets
without being internalized (Figure 1A). In contrast, agonistactivated platelets exhibited frequent images of bacteria internalization (Figure 1B). This observation led to the conclusion that platelet
activation considerably increases bacteria internalization.
Bacteria engulfment occurs in a specific subcellular compartment. To document the antigenic composition of the limiting
membrane of vacuoles that surround internalized bacteria (engulfing vacuoles), immunolabeling experiments were performed on
thin sections of thrombin-activated platelets incubated with S
aureus, by using antibodies against several platelet glycoproteins
(␣IIb␤3, P-selectin, GPIb, and fibrinogen). Within resting platelets,
␣IIb␤3 is present along the plasma membrane, the membrane of the
OCS, and the ␣-granule membrane (Figure 2A, inset); P-selectin is
restricted to the ␣-granule membrane (Figure 2B, inset); GPIb is
located mainly on plasma membrane (Figure 2C, inset). During
platelet activation, antigens redistribute in the following way:
␣IIb␤3 plasma membrane expression significantly increased and
P-selectin appeared on the plasma membrane; OCS and GPIb have
cleared from the plasma membrane and are internalized into the
OCS membrane. In our samples, upon platelet activation, OCS
membrane expressed the 3 antigens ␣IIb␤3, P-selectin, and GPIb.25
The limiting membrane of the engulfing vacuoles also expressed
␣IIb␤3 and P-selectin (Figure 2A-B), but GPIb was consistently
absent from this compartment (Figure 2C). Thus, GPIb, which is
expressed mainly in OCS after platelet activation, is apparently not
expressed in engulfing vacuoles. These results suggest that the
engulfing vacuoles exhibit a different antigenic composition from
the OCS.
In these samples, some platelets appeared to extend pseudopods
that wrapped around the bacteria. The platelet pseudopods surrounded the particle by the process of circumferential adherence
until they fully enclosed the particle in a vacuole consisting of
internalized extracellular space surrounded by plasma membrane,
in a manner that closely resembles phagocytes engulfing bacteria.
This observation suggests that an active process leads to
bacteria internalization (Figure 3A) and that passive, amorphous
passage of bacteria into the OCS is unlikely.
Finally, in platelets with 1 or 2 large vacuoles containing
bacteria, immunolabeling for fibrinogen provided evidence that
secretion of the granule contents also occurs around internalized
bacteria. Also apparent were some images demonstrating fusion of
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BLOOD, 1 JUNE 2002 䡠 VOLUME 99, NUMBER 11
ENGULFMENT OF HIV AND S AUREUS BY PLATELETS
4023
Figure 1. Effect of ADP on S aureus internalization by
platelets. (A) Washed control platelets incubated with a
S aureus suspension. Platelets remain discoid and fully
granulated, displaying no morphological signs of activation. Bacteria (arrowheads) remain in the extracellular
space and are not internalized within platelets. Original
magnification, ⫻ 14 040. (B) Washed platelets stimulated
with 10 ␮M ADP and incubated with S aureus. Some
bacteria (arrowheads) have been internalized by platelets. These platelets present signs of morphological
activation: loss of discoid shape, extension of small
pseudopods (p), dilated OCS, disappearance of cytoplasmic granules. Original magnification, ⫻ 14 040.
␣-granules either among themselves or with the endocytic vacuole
(Figure 3B-C). Finally, fusion of the engulfing vacuoles with the
OCS-containing fibrinogen also occurred (not shown). These
observations indicate that, at the final step of internalization,
bacteria appear to be in contact with granule secretory products.
Platelets and HIV interaction
HIV internalization by platelets occurs in endosomelike structures. The ultrastructural examination of washed platelets incubated with the supernatant of HIV-infected cultured cells showed
typical images of virus internalization. In the early stage of
internalization, HIV particles were found in small vacuoles tightly
surrounding 1, 2, or 3 particles, were located close to the plasma
membrane (Figure 4A), and resembled endosomal structures. Virus
particles were also found in the dilated channels of OCS, possibly
following their fusion with the engulfing vacuoles (Figure 4B-C).
This process resembled what had been observed with bacteria.
HIV internalization occurs preferentially in activated platelets. Interestingly, viral particles were observed exclusively in
platelets undergoing secretion and displaying morphological activa-
tion signs: uneven surface, extension of pseudopods, degranulation, and dilated OCS (Figure 4A-C).
Specific uptake of HIV by platelets. HIV identification was
also performed by immunogold labeling on ultrathin cryosections
of platelets incubated with HIV particles, with the use of a pool of 3
monoclonal antibodies directed against the core protein p24. This
technique was sensitive enough to specifically detect a single viral
particle within the whole platelet cytoplasmic area (Figure 5A)
without any unspecific labeling.
This technique was also performed on the supernatant of
infected PBMCs used for platelet incubation. It showed that the
proportion of viral particles in the culture supernatant was quite
low in terms of cellular debris (Figure 5B). This tends to
demonstrate that platelets selectively take up HIV particles,
preferentially to cellular debris.
Ultrastructural aspect of platelet-HIV interaction in vivo. An
ultrastructural study of isolated platelets from a patient with AIDS,
high viremia level, and thrombocytopenia was performed. In this
sample, we observed a viral particle tightly enclosed within a small,
typical endocytic vacuole (Figure 6). The particle exhibited the
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YOUSSEFIAN et al
BLOOD, 1 JUNE 2002 䡠 VOLUME 99, NUMBER 11
Figure 2. Immunogold labeling of thrombin-activated platelets incubated with S aureus. (A) In platelets containing bacteria (B), ␣IIb␤3 labeling (arrowheads) is prominent
along the plasma membrane (pm) and the OCS membrane. Like OCS, the limiting membrane of the engulfing vacuoles (v) is heavily labeled. Original magnification, ⫻ 23 250.
Inset: In control platelets, ␣IIb␤3 is immunodetected along the plasma membrane and the ␣-granule membrane. Inset original magnification, ⫻ 34 100. (B) P-selectin
(arrowheads) is consistently detected along the plasma membrane (pm) and the OCS, as expected, following platelet activation. The membrane of the engulfing vacuoles
surrounding the bacteria is also labeled for P-selectin. Original magnification, ⫻ 23 250. Inset: In control platelets, P-selectin is restricted to the ␣-granular membrane and is
absent from plasma membrane. Inset original magnification, ⫻ 34 100. (C) GPIb (arrowheads), which is immunodetected on the OCS membrane, is not found within the
membrane of the engulfing vacuoles, showing that this compartment is distinct from the OCS. Noteworthy, GPIb is absent from the plasma membrane (pm), showing its
redistribution into the OCS, a distribution pattern that is well established in activated platelets. Original magnification, ⫻ 23 250. Inset: In control platelets, GPIb is located
mainly on the plasma membrane. Inset original magnification, ⫻ 34 100.
size, shape, and dense core characteristic of HIV. The results
obtained in vivo tend to confirm the in vitro data and indicate that
HIV endocytosis into platelets may occur during HIV infection.
Discussion
The mechanism by which platelets interact with infectious
microorganisms is poorly understood. In this study, we have
focused on the interaction of washed normal platelets with either
bacteria (S aureus) or viral particles (HIV). The susceptibility of
bacteria internalization was initially studied under conditions
that prevent platelet aggregation (washed platelets and washed
bacteria). Although engulfment of bacteria by resting platelets
was rare, the few platelets in which internalization was evident
displayed the characteristics of platelet activation. However,
under these experimental conditions, no major platelet activation was induced by the bacteria.
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BLOOD, 1 JUNE 2002 䡠 VOLUME 99, NUMBER 11
ENGULFMENT OF HIV AND S AUREUS BY PLATELETS
4025
Figure 3. Thrombin-activated platelets incubated with S aureus, immunolabeled for fibrinogen (arrowheads). (A) Platelet pseudopods surround the particle by a
process of circumferential adherence. Fibrinogen release in OCS indicates platelet activation. Original magnification, ⫻ 37 200. (B) Several ␣-granules (a) fuse together and
their fibrinogen content is released into the engulfing vacuole (v). Original magnification, ⫻ 27 900. (C) The ␣-granule fibrinogen is detected within the engulfing vacuole, in
close contact with the bacterium. Original magnification, ⫻ 44 950.
To determine whether platelet activation triggered or enhanced
bacterial uptake, platelet agonists were added in the incubation
medium. These experiments showed that platelet activation greatly
increases bacteria internalization.
The first step of phagocytosis is bacterial adherence to the cell
surface, which usually requires the participation of a receptor and a
ligand. Recently, it has been shown that the receptor for the
complement component C1q (C1qR/p33) is recognized by S aureus
protein26; this indicates that C1qR could be a potential binding site
for S aureus. It is noteworthy that C1qR/p33 is expressed on
platelet surface after platelet activation.27 In addition, thrombospondin, which has been described as an S aureus–adherence
mediator, is also secreted from the ␣-granules upon activation.28
Therefore, these studies provide additional evidence that platelet
activation can facilitate S aureus internalization.
To elucidate the mechanisms of S aureus interaction with
platelets, we proceeded to study the subcellular distribution of
receptors in platelets engulfing bacteria. Immunolabeling experiments for ␣IIb␤3, GPIb, P-selectin, and fibrinogen were performed.
These experiments confirmed that the platelets that had engulfed
bacteria displayed classical activation signs (GPIb internalization,
P-selectin surface expression, and fibrinogen release).
Examination of the antigenic composition of the engulfing
vacuoles suggested that they express a distinct composition from
the OCS since GPIb, which is present in OCS, was not detected
within the engulfing vacuoles. In fact, the antigenic composition of
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YOUSSEFIAN et al
BLOOD, 1 JUNE 2002 䡠 VOLUME 99, NUMBER 11
Figure 4. Morphological study of washed platelets incubated with HIV particles. (A) Internalization of HIV particles in endosomelike structures. In the early stage of
internalization, HIV particles are found in some characteristic small vacuoles as endosomelike structures tightly surrounding 1 or 2 particles (vi), and located close to the plasma
membrane (pm). a indicates ␣-granules. Original magnification, ⫻ 36 800; inset original magnification, ⫻ 55 200. (B) (C) HIV particles (vi) are further retrieved in the OCS.
These platelets show morphological activation signs: spherical shape, bristled surface with pseudopods (arrows), dilated OCS. mi indicates mitochondria. Original
magnification, ⫻ 41 850.
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BLOOD, 1 JUNE 2002 䡠 VOLUME 99, NUMBER 11
ENGULFMENT OF HIV AND S AUREUS BY PLATELETS
4027
Figure 5. Immunogold detection of HIV on ultrathin
cryosections. (A) In platelets incubated with the supernatant of HIV-infected cultured PBMCs, immunogold
labeling for the HIV core protein p24 can specifically and
sensitively identify a virionlike particle (vi) that has been
internalized in the platelet. This allows its definite identification as an HIV particle. Virtually no background labeling is observed. Original magnification, ⫻ 40 250; inset
original magnification, ⫻ 86 250. (B) Immunogold labeling for p24 was applied on the supernatant of HIVinfected cultured PBMCs: viral particles (arrows) are rare
and are scattered among abundant cellular debris. Original magnification, ⫻ 46 200.
the engulfing vacuoles is the same as the plasma membrane after
activation (expression of ␣IIb␤3 and P-selectin, but not GPIb).25
This indicates that the engulfing vacuoles are probably formed by
plasma membrane invagination (endocytosis) after platelet activation. It has been shown that GPIb is associated with cytoskeletal
actin and that it is responsible for maintenance of platelet discoid
form. The clearance of GPIb from the platelet plasma membrane
upon activation accompanies classical shape changes.29 In contrast,
␣IIb␤3 becomes associated with cytoplasmic actin filaments upon
activation.30 Thus, the interaction of the 2 surface receptors with
cytoskeletal components could be implicated in the contractile
events necessary for bacteria internalization.
In platelets with large vacuoles containing bacteria, fibrinogen
labeling suggests that ␣-granular fusion with the engulfing vacuoles occurs. This results in granular secretion around bacteria, thus
allowing interaction of both bacteria and ␣-granule proteins.
Examination of platelets incubated with the supernatant of HIVinfected PBMC culture shows intracellular HIV particles with their
characteristic size, shape, and eccentric dense core.31 At the early step of
internalization, HIV particles were tightly surrounded by endosomelike
structures and located close to the plasma membrane. These images are
very similar to those associated with HIV transcytosis in epithelial cells.
Transcytosis is a mechanism that involves translocation of HIV particles
through epithelial cells by endocytosis without infecting the
epithelium itself.32,33 Transcytosis in platelets differs from epithelial cells because platelets are isolated, secretory cells. In addition,
endosomelike structures containing HIV particles in platelets
would be expected to fuse with the OCS as observed. Remarkably,
platelets that contained intracellular viruses also displayed activation signs. Granular components would then also be secreted on
HIV particles, in a manner similar to the process that occurs in
bacteria internalization by platelets.
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BLOOD, 1 JUNE 2002 䡠 VOLUME 99, NUMBER 11
YOUSSEFIAN et al
Figure 6. Ultrastructural study of platelets from a
patient with AIDS and thrombocytopenia. A foreign
particle with the size, shape, and dense core characteristic of HIV is detected within an endocytic vacuole in a
circulating platelet of this patient. Original magnification,
⫻ 48 050; inset original magnification, ⫻ 96 100.
Immuno-EM using a pool of monoclonal antibodies against the
core protein p24 was demonstrated to be a specific and sensitive
technique since we could detect a single viral particle in the whole
platelet surface. It also showed that HIV particles were rare in the
supernatant of infected platelets, suggesting that the cells could
selectively internalize HIV virions preferentially over cellular
debris. Finally, examination of HIV viremia in various plasma
samples more or less contaminated with platelets showed an
increase of HIV RNA copy number per unit of plasma volume
parallel to the intensity of platelet contamination. Finally, examination of platelets of a patient with AIDS allowed us to validate the
results we obtained in vitro. Our observations suggest that this
phenomenon can occur in HIV-infected patients and may therefore
be a cause of platelet destruction and thrombocytopenia.
In analogy with the phagocytic process, engulfing vacuoles can
be compared to phagosomes, and the fusion of these vacuoles with
granules can be compared to the phagosome-lysosome fusion,
which permits the release of granular materials onto the microorganisms. The granular components exhibit microbicidal and antiviral
activity. Indeed, previous studies have shown the existence of 2
microbicidal proteins from human blood platelets called thrombocidins34 and have shown that platelets are a source of RANTES
(regulate upon activation normal T-cell–expressed and secreted)
chemokines,35-37 which have been known for their suppressive
effects on HIV infection,38 even before the discovery of HIV CCR5
coreceptor. These proteins, stored in the ␣-granules, are released in
the endocytic compartment in contact with internalized particles.
Platelet ␣-granules also contain ␤-thromboglobulin and platelet
factor–4, which have been shown to be platelet-derived CXC
chemokines and to contribute to coordinate recruitment and
activation of neutrophils in response to acute tissue injury.39 These
data show the potential antimicrobial role of platelets and the
objective of microorganism internalization by platelets. We have
also shown that microorganism internalization specifically occurs
in activated platelets that express P-selectin on their surface,
enabling their attachment to phagocytes, such as polymorphonuclear leukocytes, monocytes, and macrophages,40 that bear
P-selectin glycoprotein ligand–1. This could also contribute to the
thrombocytopenia. Therefore, this study suggests that platelets may
assist phagocytes in the clearance of microorganisms. However,
neither killing nor digestion of microorganisms within platelets
has so far been demonstrated. Thus, we have avoided using the
term phagocytosis and have used “engulfment” and “internalization” instead.
An alternative hypothesis would be that endocytosis of HIV by
platelets would be a pathway that HIV could use to evade either the
immune system or anti-HIV treatment. Therefore, further studies
need to be performed to elucidate the incidence of platelet/
microorganism interaction and its effect on the general capacity of
the human host to defend against infection.
In conclusion, our results demonstrate that (1) platelet activation greatly facilitates microorganism uptake; (2) internalization
occurs in endosomelike structures that are different from the OCS,
in a probably selective and active manner; and (3) platelets may
play an essential role in host defense.
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From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
2002 99: 4021-4029
doi:10.1182/blood-2001-12-0191 originally published online
April 30, 2002
Host defense role of platelets: engulfment of HIV andStaphylococcus
aureus occurs in a specific subcellular compartment and is enhanced by
platelet activation
Tayebeh Youssefian, Arnaud Drouin, Jean-Marc Massé, Josette Guichard and Elisabeth M. Cramer
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