Exposure of platelet fibrinogen receptors by a monoclonal antibody to CD9 antigen

Hato, Takaaki; Ikeda, K; Yasukawa, Masaki; Watanabe, Akito; Kobayashi, Yoshinari

doi:10.1182/blood.v72.1.224.224

Cited by 60 publications

(19 citation statements)

References 28 publications

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“…19 and BU-16) are of the IgG2a subclass, and both are also lytic. 25,26 In most cases, the proteolytic fragments of these antibodies lack ing the Fc domain do not activate platelets, but, when tested, 1,6,27,28 block the activation by the native mole cule. The TP-82 seems to be an exception, since the F(ab')2 fragments (but not the Fab fragments) were re ported to activate platelets.…”

Section: Cd9 Antigenmentioning

confidence: 99%

Anti-Platelet Antibody Interactions with Fcγ Receptor

Rubinstein¹,

Boucheix²,

Worthington³

et al. 1995

Semin Thromb Hemost

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In the course of characterizing monoclonal antibod ies (mAbs) and their interactions with different blood cell types, it was found in the early 1980s that platelet activa tion could be induced by certain mAbs that recognized platelet antigens. 1,2 One of the first activating mAbs to be discovered belongs to a cluster of mAbs (designated CD9) directed to a platelet surface antigen of 24 kDa 1 discovered through screening for acute lymphoblastic leukemia antigens. 3 This initial report was followed by the finding by several groups that a large number of the CD9 mAbs triggered platelet activation. In addition re ports describing mAbs against GPIIb/IIIa and other anti gens that were also potent platelet activators began to appear in the literature. Summaries of most of these find ings were presented at the Leukocyte Typing Workshops III and IV. 4 ' 5 In these initial reports the activation by the mAb was attributed to the cross-linking or occupancy of the target antigen recognized by these mAbs. Indeed, the primary basis for that conclusion was the apparent specificity of this interaction, since most mAbs directed to other plate let antigens have no effect on platelet function. 4 ' 5 The conclusions drawn from these earlier studies were that each of these target antigens had a specific role in platelet activation. However, recent studies have established that mAbs to various platelet antigens activate through an interaction of their Fc domains with the platelet Fc recep tor. The purpose of this review is to describe the proper ties of the target antigens and mAbs for which there is extensive published data with respect to platelet activa tion and to suggest common activation mechanisms.

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Section: Cd9 Antigenmentioning

confidence: 99%

Anti-Platelet Antibody Interactions with Fcγ Receptor

Rubinstein¹,

Boucheix²,

Worthington³

et al. 1995

Semin Thromb Hemost

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“…CD9 is an abundant platelet membrane protein, of the same order as α IIb β $ (approx. 45 000 molecules per cell) [11,12], but with an uncertain function. CD9 and α IIb β $ also share a similar cellular distribution in the membrane of platelet α-granules containing fibrinogen and von Willebrand's Factor [13].…”

Section: Introductionmentioning

confidence: 99%

Analysis of the tetraspanin CD9–integrin αIIbβ3 (GPIIb-IIIa) complex in platelet membranes and transfected cells

Indig

Dı́az-González

Ginsberg

1997

Biochemical Journal

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The platelet integrin, alphaIIbbeta3 (GPIIb-IIIa), and the tetraspanin, CD9, are integral membrane proteins that are abundant in platelet membranes. We have identified several proteins, including CD9, which were co-precipitated by anti-alphaIIbbeta3 antibody from untreated, resting platelets that were solubilized with the poly(oxyethylene) non-ionic detergent, Brij-35. Immunoblot and quantitative immunoprecipitation showed that the association of alphaIIbbeta3 with CD9 is specific and stoichiometric. The interaction between CD9 and alphaIIbbeta3 is probably hydrophobic, as Triton X-100 and hydrophobic detergents of the Brij series completely dissociated the CD9-alphaIIbbeta3 complex. Recombinant CD9 and alphaIIbbeta3 can associate after transfection into Chinese hamster ovary cells, as seen by co-immunoprecipitation and co-localization in the periphery of spreading cells and in the lamellipodia of cells plated on fibrinogen. This co-localization is absent from focal adhesions. Furthermore, anti-CD9-coated latex beads clustered alphaIIbbeta3 with CD9. This work indicates that the tetraspanin, CD9, is associated with beta3 integrins in resting platelets and transfected cells.

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“…We propose that secreted ADP would serve to Vol. 266 initiate MLC phosphorylation independent of TxA2 synthesis (Daniel et al, 1984), as well as to cause direct expression of fibrinogen receptors supporting platelet aggregation (Hato et al, 1988). Thus, in the presence of both aspirin and apyrase, these activation pathways are blocked.…”

Section: Discussionmentioning

confidence: 99%

“…Bivalent interaction may be required for platelet activation leading to aggregation and granule secretion, since these responses are not elicited by univalent Fab fragments of ALB-6 (Boucheix et al, 1983), Ba2 (Brown et al, 1984) and FMC8 and FMC56 MAbs (Gorman et al, 1985). Another MAb (PMA2) against the CD9 antigen has recently been shown to trigger fibrinogenreceptor expression and platelet aggregation solely through platelet activation (Hato et al, 1988). The present study confirms the report by Rendu et al (1987) that both an aspirin-sensitive thromboxane A2 (TxA2) pathway and an aspirin-insensitive pathway for secretion of ADP are responsible for platelet aggregation induced by MAbs to the CD9 antigen (ALB-6 and SYB-1).…”

Section: Introductionmentioning

confidence: 99%

Stimulus-response coupling in human platelets activated by monoclonal antibodies to the CD9 antigen, a 24 kDa surface-membrane glycoprotein

Carroll

Worthington

Boucheix

1990

Biochemical Journal

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The CD9 molecule is a 24 kDa surface-membrane glycoprotein present on platelets and a variety of haematopoetic and non-haematopoetic tissues. In the present study we utilized specific inhibitors of thromboxane A2 (TxA2) formation (aspirin), protein kinase C [H-7 [1-(5-isoquinolinesulphonyl)-2-methylpiperazine]] and autocrine stimulation by secreted ADP (apyrase) to modify platelet activation by a monoclonal antibody ALB-6 to the CD9 antigen. This activation is only partially inhibited by aspirin alone but, in combination with either H-7 or apyrase, more than 50% inhibition of platelet aggregation and secretion was observed. This combination of inhibitors was also required to inhibit effectively the phosphorylation of myosin light chain and the 47 kDa substrate of protein kinase C. Intracellular Ca2+ flux monitored by the fluorescent dye fura-2 showed that this was almost completely mediated by the aspirin-sensitive TxA2 pathway. We suggest that the aspirin-insensitive pathway is primarily mediated by phospholipase C formation of diacylglycerol to activate protein kinase C. The inhibition by apyrase suggests a strong dependency on autocrine stimulation by secreted ADP to fully activate both phospholipase C and express fibrinogen-binding sites mediating platelet aggregation. This alternate pathway of phospholipase C activation by ALB-6 may be mediated by cytoplasmic alkalinization [monitored by SNARF-1 (5'(6')-carboxy-10-bismethylamino-3-hydroxy-spiro-[7H- benzo[c]xanthine-1',7(3H)-isobenzofuran]-3'-one) fluorescence of the dye]. Both activation pathways are dependent on intact antibodies, since F(ab')2 fragments of SYB-1, a monoclonal antibody against the CD9 antigen with activation characteristics identical with those of ALB-6, do not elicit activation. Besides thrombin, collagen is another physiological agonist shown to induce aspirin-insensitive activation. Similarities to ALB-6 in collagen sensitivity to apyrase in combination with aspirin inhibitors were noted with respect to aggregation and secretion, as well as a complete block of Ca2+ flux by aspirin. However, it is unlikely that collagen activation is mediated by the CD9 antigen, since SYB-1 F(ab')2 fragments had no effect on collagen activation and aspirin also completely blocked the alkalinization response to collagen, in contrast with ALB-6.

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Exposure of platelet fibrinogen receptors by a monoclonal antibody to CD9 antigen

Cited by 60 publications

References 28 publications

Anti-Platelet Antibody Interactions with Fcγ Receptor

Anti-Platelet Antibody Interactions with Fcγ Receptor

Analysis of the tetraspanin CD9–integrin αIIbβ3 (GPIIb-IIIa) complex in platelet membranes and transfected cells

Stimulus-response coupling in human platelets activated by monoclonal antibodies to the CD9 antigen, a 24 kDa surface-membrane glycoprotein

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