Platelet activation and inhibition of malarial cytoadherence by the anti-CD36 IgM monoclonal antibody NL07

Alessio, Massimo; Greco, NJ; Primo, Luca; Ghigo, Dario; Bosìa, Amalia; Tandon, NN; Ockenhouse, CF; Ga, Jamieson; Malavasi, Fabio

doi:10.1182/blood.v82.12.3637.bloodjournal82123637

Cited by 5 publications

(8 citation statements)

References 2 publications

(3 reference statements)

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“…Recently, an antibody against GP IV (CD36) was found in most TTP patients, which induced platelet activation in vitro (Tandon et al, 1994). An anti-CD36 IgM monoclonal antibody which activated washed platelets in the presence of complement and external Ca 2þ was also described (Alessio et al, 1993). Unusually large VWF multimers (ULVWF) released from injured endothelial cells have also been implicated as a PAPF in TTP (Moake & Eisenstaedt, 1994).…”

Section: Discussionmentioning

confidence: 99%

Thrombotic thrombocytopenic purpura plasma enhances platelet–leucocyte interaction in vitro

Valant

Horstman

et al. 1998

Br J Haematol

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Summary.In thrombotic thrombocytopenic purpura (TTP), intravascular platelet aggregation and formation of plateletrich thrombi impair the microcirculation. TTP plasma has been shown to induce aggregation of normal platelets in vitro. The present study investigates the formation of activated platelet aggregates (aPAg) induced by TTP plasma, with particular attention to their binding to leucocytes (LPAg). Results were compared with the effects of plasmas from normal controls (CTL) and from patients with immune thrombocytopenic purpura (ITP) or thrombosis (THR). Following addition of test plasma to normal whole blood (WB), aPAg and LPAg were assayed by flow cytometry using mAbs against CD41 (platelet marker), CD62p (platelet activation marker) and CD45 (pan-leucocyte marker). Compared to control plasma, TTP plasma was more potent than ITP or THR plasma in increasing aPAg; only TTP plasma significantly promoted leucocyte binding to give increased LPAg. Prior removal of neutrophils (PMN) from WB by beads coated with anti-CD15 mAb largely prevented formation of aPAg and LPAg. However, TTP plasma added to normal platelet-rich plasma significantly increased aPAg, which suggested possible hindrance of aPAg formation by erythrocytes and other leucocytes in PMN-depleted blood. We concluded that TTP plasma was most potent in the induction of aPAg and unique in promoting LPAg formation in WB. Neutrophils, and not other leucocytes, appear to be essential for LPAg formation. Enhanced PMN-platelet interaction in the microcirculation may facilitate platelet adhesion to vessel walls and promote the formation of platelet-rich microthrombi in TTP.

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Section: Discussionmentioning

confidence: 99%

Thrombotic thrombocytopenic purpura plasma enhances platelet–leucocyte interaction in vitro

Valant

Horstman

et al. 1998

Br J Haematol

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“…Puri®ed CD36, as well as murine monoclonal antibodies against CD36, inhibit the binding of infected erythrocytes to endothelial cells and cell lines bearing surface CD36 in vitro (Tandon et al 1989b, Alessio et al 1993, Asch et al 1993. With the aim of producing a molecule capable of inhibiting malaria cytoadherence and also effective in triggering antibody-dependent cellular cytotoxicity and phagocytosis, we generated a soluble chimeric molecule by fusion of extracellular domains of CD36 with human immunoglobulin domains.…”

Section: Introductionmentioning

confidence: 99%

CD36 folding revealed by conformational epitope expression is essential for cytoadherence of Plasmodium falciparum‐infected red blood cells

Gruarin

Monte

Alessio

2000

Parasite Immunology

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CD36 is a membrane glycoprotein and a putative scavenger receptor expressed by several cell types. In capillary endothelial cells, it mediates the adherence of erythrocytes infected with Plasmodium falciparum. The CD36 sequence contains two hydrophobic domains located at the amino-and carboxyl-termini of the protein, but the topology of this protein and the functional significance of these domains are still not clearly defined. We generated soluble CD36-IgG chimeric molecules by fusion of the extracellular domains of CD36 with human immunoglobulin domains. The construct containing the N-terminal hydrophobic domain of CD36 was completely retained intracellularly as membrane-associated molecule, suggesting that the N-terminal hydrophobic domain of the CD36 is a real transmembrane domain and that CD36 has hairpin topology. A small amount of the CD36-IgG chimeric construct lacking both transmembrane domains escaped retention, was correctly processed, and accumulated in the extracellular medium as a soluble molecule. This CD36-IgG construct failed to bind Plasmodium falciparum-infected erythrocytes. Using monoclonal antibodies specific for either conformational or structural epitopes, we demonstrate that failure of this CD36-IgG construct to bind infected erythrocytes was due to incorrect folding of the soluble chimeric molecule.

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“…Phosphorylation of the 64 kDa protein may be specifically related to the induction of platelet shape change, since in anti-PTAl-stimulated cells this response was not followed by aggregation/secretion. The absence of tyrosine phosphorylation and functional responses to the anti-CD36 mAb suggests that the reported agonist effects of this particular mAb (Aiken et al, 1990;Alessio et al, 1993) entirely depend on FcyRII signalling.…”

Section: Discussionmentioning

confidence: 99%

“…It is unlikely that the number of surface molecules accounts for the failure of cross-linked anti-CD36 and anti-PTAI mAb to induce aggregation. FcyRII is represented on the platelet membrane in much lower numbers [approximately 2000[approximately molecules/ platelet (McCrae et al, 1990] than is CD36 [approximately 12000 (Aiken et al, 1990;Alessio et al, 1993)], yet the crosslinking of FcyRII on normal and thrombasthenic platelets induced aggregation as well as a-granule and dense-granule release. Moreover, it is unlikely that differences in the cytoskeletal associations of CD9, CD42, CD36, gpIIb/IIIa and PTAI account for the differences in the ability of the respective mAb (to these antigens) to induce aggregation.…”

Section: Discussionmentioning

confidence: 99%

“…However, previous work by us and others has demonstrated that the target antigens of several mAb themselves have active signalling roles (Morel et al, 1989;Slupsky et al, 1992;Griffith et al, 1991;Alessio et al, 1993), and that in the generation of an antigenic signal, FcyRII has an anchorage or cross-linker function (Slupsky et al, 1992;Anderson et al, 1991 ;Rubinstein et al, 1991b;Horsewood et al, 1991). Therefore, to avoid signalling associated with FcyRII engagement, it is necessary to block this receptor and to provide an alternative cross-linking of antigen-bound mAb.…”

Section: Cd9 Cd41 and Cd42 Mab Induce Platelet Aggregation Independementioning

confidence: 96%

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The Platelet Antigens CD9, CD42 and Integrin α_IIbβ_IIIa Can be Topographically Associated and Transduce Functionally Similar Signals

Slupsky

Kamigutt

Rhodes

et al. 1997

European Journal of Biochemistry

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Investigation of the specific effects of different mAb known to stimulate platelets (agonist mAb) is complicated by interaction of the Fc portion of these mAb with the platelet FcyRII. This has led to the conclusion that nearly all agonist-mAb-induced activation of platelets is mediated by this receptor. However, the target antigen-mediated signal can be analysed provided that the effects of FcyRII engagement can either be reduced or eliminated. We have therefore blocked platelet FcyRll with IV.3 Fab fragments (an anti-FcyRII mAb), and stimulated the platelets by cross-linking intact agonist mAb with F(ab')> fragments of an Fc-specific anti-mouse antibody. By analysing functional platelet responses and proteintyrosine phosphorylation, we found that such non-FcyRII-mediated cross-linking of CD9, CD42 and glycoprotein (gp) IIb/IIIa generates closely similar signals. Since this may indicate molecular associations, we analyzed the surface topography of platelets using the chemical cross-linking agent dithiobis(su1fosuc-cinimidyl propionate). We found that a proportion of CDY, gpIIb/IIIa and CD42 molecules associate with each other on the platelet surface membrane. Thus, our results suggest that these antigens are able to form a larger molecular complex and induce similar signals. Furthermore, cross-linking of CD9 and CD42 stimulated thrombasthenic platelets completely lacking gpIIb/IIIa. These data therefore indicate that CDY and CD42 can signal independently of gpIIb/IIIa, and that signals generated by all these molecules may converge on a common pathway.Keywords: glycoprotein Tb ; integrin ; CD9 ; transmembrane-4 superfamily ; signal transduction.Many cell receptors are now known to be multicomponent complexes involving ligand-binding and signalling proteins. Members of the transmembrane-4 superfamily (or tetraspan superfamily) of membrane proteins, which includes CD9 , are frequently found within such complexes, where they are thought to participate in receptor signalling (reviewed by Wright and Tomlinson, 1994). The B-cell and T-cell antigen receptors are particularly good examples of such multicomponent structures (Matsumoto et al., 1993 ;Imai et al., 1995).Integrin heterodimers can form complexes with other membrane proteins, including a transmembrane-4 protein, CD9 (Slupsky et al., 1989;Rubinstein et al., 1994;Nakamura et al., 1995). Thus, in stimulated platelets, the principal integrin, glycoprotein (gp)IIb/IIIa (also known as a , r h /~3 , CD41/CD61), has been shown by chemical cross-linking to be associated with CD9 (Slupsky et al., 1989). In addition, there is evidence that gpIIb/IIIa and gpIb/TX [CD42b/CD42a; a receptor for von Willebrand factor and thrombin (Roth, 1991 ;Gralnick et al., 1994)] may also be associated (Fox, 1985;Davies and Palek, 1982;Jung and Moroi, 1983 These observations raise the possibility that gpIIb/IIIa, gpIbl IX and CD9 can all associate into multicomponent adhesion/ signalling receptor complexes. In the present paper, we provide evidence from mAb-probing and chemical-cross-linki...

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Platelet activation and inhibition of malarial cytoadherence by the anti-CD36 IgM monoclonal antibody NL07

Cited by 5 publications

References 2 publications

Thrombotic thrombocytopenic purpura plasma enhances platelet–leucocyte interaction in vitro

Thrombotic thrombocytopenic purpura plasma enhances platelet–leucocyte interaction in vitro

CD36 folding revealed by conformational epitope expression is essential for cytoadherence of Plasmodium falciparum‐infected red blood cells

The Platelet Antigens CD9, CD42 and Integrin α_IIbβ_IIIa Can be Topographically Associated and Transduce Functionally Similar Signals

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Platelet activation and inhibition of malarial cytoadherence by the anti-CD36 IgM monoclonal antibody NL07

Cited by 5 publications

References 2 publications

Thrombotic thrombocytopenic purpura plasma enhances platelet–leucocyte interaction in vitro

Thrombotic thrombocytopenic purpura plasma enhances platelet–leucocyte interaction in vitro

CD36 folding revealed by conformational epitope expression is essential for cytoadherence of Plasmodium falciparum‐infected red blood cells

The Platelet Antigens CD9, CD42 and Integrin αIIbβIIIa Can be Topographically Associated and Transduce Functionally Similar Signals

Contact Info

Product

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The Platelet Antigens CD9, CD42 and Integrin α_IIbβ_IIIa Can be Topographically Associated and Transduce Functionally Similar Signals