The action of calcium-dependent protease on platelet surface glycoproteins

McGowan, Eleanor B.; Yeo, Kiang-Teck; Detwiler, Thomas C.

doi:10.1016/0003-9861(83)90373-9

Cited by 89 publications

(29 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It may be either internalized following platelet activation [20] or shed due to cleavage by the metalloproteinase TACE=ADAM 17 [13]. A potential role of the calcium-dependent protease calpain has also been reported [22]. Our results suggest that metalloproteinase participate to the loss of GPIba in culture-derived PLPs.…”

Section: Discussionmentioning

confidence: 48%

Glycoprotein Ibα Receptor Instability Is Associated with Loss of Quality in Platelets Produced in Culture

Robert

Boyer

Pineault

2011

Stem Cells and Development

View full text Add to dashboard Cite

The development of culture processes for hematopoietic progenitors could lead to the development of a complementary source of platelets for therapeutic purposes. However, functional characterization of culture-derived platelets remains limited, which raises some uncertainties about the quality of platelets produced in vitro. The aim of this study was to define the proportion of functional platelets produced in cord blood CD34+ cell cultures. Toward this, the morphological and functional properties of culture-derived platelet-like particles (PLPs) were critically compared to that of blood platelets. Flow cytometry combined with transmission electron microscopy analyses revealed that PLPs formed a more heterogeneous population of platelets at a different stage of maturation than blood platelets. The majority of PLPs harbored the fibrinogen receptor αIIbβ3, but a significant proportion failed to maintain glycoprotein (GP)Ibα surface expression, a component of the vWF receptor essential for platelet functions. Importantly, GPIbα extracellular expression correlated closely with platelet function, as the GPIIb+ GPIbα+ PLP subfraction responded normally to agonist stimulation as evidenced by α-granule release, adhesion, spreading, and aggregation. In contrast, the GPIIb+ GPIbα⁻ subfraction was unresponsive in most functional assays and appeared to be metabolically inactive. The present study confirms that functional platelets can be generated in cord blood CD34+ cell cultures, though these are highly susceptible to ectodomain shedding of receptors associated with loss of function. Optimization of culture conditions to prevent these deleterious effects and to homogenize PLPs is necessary to improve the quality and yields of culture-derived platelets before they can be recognized as a suitable complementary source for therapeutic purposes.

show abstract

Section: Discussionmentioning

confidence: 48%

Glycoprotein Ibα Receptor Instability Is Associated with Loss of Quality in Platelets Produced in Culture

Robert

Boyer

Pineault

2011

Stem Cells and Development

View full text Add to dashboard Cite

show abstract

“…Remold-O'Donnell et al (1993) reported that calpain released from disrupted normal platelets can cleave lymphocyte CD43 and suggested that this may be an important mechanism for the manifestations of WAS. Calpain, a Ca 2+ -dependent neutral protease, is known also to cleave platelet surface GPIb (McGowan et al, 1983), and although GPIb expression was found to be normal, it is possible that this, or another, protease may account for the observed reduction in GPIIbIIIa and GPIV expression on WAS platelets. Whether the platelet glycoprotein abnormalities per se result in accelerated platelet destruction and thrombocytopenia is, however, not known.…”

Section: Discussionmentioning

confidence: 99%

Flow cytometric analysis of platelets from childrenwith the Wiskott‐Aldrich syndrome reveals defects in platelet development, activation and structure

Semple

Siminovitch

Mody³

et al. 1997

Br J Haematol

View full text Add to dashboard Cite

Summary. The pathophysiology of platelet dysfunction in the Wiskott-Aldrich immune deficiency syndrome (WAS) remains unclear. Using flow cytometry, we have characterized the functional properties of platelets from 10 children with WAS. Patients with WAS had thrombocytopenia, small platelets, increased platelet-associated IgG and reduced platelet-dense granule content. Levels of reticulated 'young' platelets were normal in the WAS patients. Although the mean numbers of platelet glycoprotein (GP) Ib, GPIIbIIIa and GPIV molecules per platelet appeared lower in WAS patients than in healthy controls, analysis of similar-sized platelets revealed the mean number of GPIb molecules per platelet to be comparable in patients and normal controls. Surface GPIIbIIIa and GPIV expression was, however, significantly lower on the WAS platelets than on normal platelets. Compared with normal platelets, WAS platelets showed a reduced ability to modulate GPIIbIIIa expression following thrombin stimulation. In addition, thrombin-and ADPinduced expression of CD62P and CD63 was defective in WAS platelets. Phallacidin staining of the WAS platelets revealed less F-actin content than in normal platelets. Together, these data suggest that the reduced platelet number and function in WAS reflects, at least in part, a defect in bone marrow production as well as an intrinsic platelet abnormality.

show abstract

“…Glycocalicin, the water soluble proteolytic fragment of the a chain of GPIb (GPIba) released by the endogenous platelet calcium-activated protease (7)(8)(9)(10), was purified in a similar manner. The only difference was that washed platelets were disrupted in a detergent-free buffer (10 mM Tris-HCI/150 mM NaCl/2 mM CaCl2/0.1 mM phenylmethylsulfonyl fluoride/ 0.02% NaN3, pH 7.4) and the supernatant obtained after centrifugation at 100,000 x g for 30 min at 4°C was used in the affinity purification procedure.…”

mentioning

confidence: 99%

Amino acid sequence of the von Willebrand factor-binding domain of platelet membrane glycoprotein Ib.

Titani¹,

Takio²,

Handa³

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

140

View full text Add to dashboard Cite

We report the amino acid sequence of a 299-residue segment from the a chain of the human platelet membrane glycoprotein lb. This includes the complete sequence of the amino-terminal tryptic fragment of 290 residues comprising the von Willebrand factor-binding domain. Two primary sets of overlapping fragments were obtained by cleavage of the S-carboxymethylated protein at methionyl and lysyl bonds following treatment with cyanogen bromide and Achromobacter protease I, respectively. Additional fragments were obtained by treatment of native glycocalicin with trypsin, Staphylococcus aureus V8 protease, and Serratia marcescens protease. Analysis of all these fragments provided data that allowed determination of the continuous sequence corresponding to approximately half of the a-chain polypeptide. This region of glycoprotein lb is largely hydrophobic and contains only two N-linked and one 0-linked carbohydrate chains. A hydrophilic region exists between residues 215 and 299, which contains a cluster of 10 negatively charged residues at 269-287. This area is likely to attract positively charged molecules. The hydrophilic, highly glycosylated (at serine and threonine residues) region corresponding to the previously described "macroglycopeptide" and representing the carboxyl-terminal halfof the a chain is likely to begin at residue 292. The determined sequence of the a chain of glycoprotein lb contains a region (residues 29-193) with seven repeats, which is indicative of gene duplication and is highly homologous to human leucine-rich a2-glycoprotein. This protein sequence agrees completely with that deduced from the cDNA sequence reported by Lopez et al.

show abstract

The action of calcium-dependent protease on platelet surface glycoproteins

Cited by 89 publications

References 27 publications

Glycoprotein Ibα Receptor Instability Is Associated with Loss of Quality in Platelets Produced in Culture

Glycoprotein Ibα Receptor Instability Is Associated with Loss of Quality in Platelets Produced in Culture

Flow cytometric analysis of platelets from childrenwith the Wiskott‐Aldrich syndrome reveals defects in platelet development, activation and structure

Amino acid sequence of the von Willebrand factor-binding domain of platelet membrane glycoprotein Ib.

Contact Info

Product

Resources

About