Chemistry Reference
In-Depth Information
VWF - , complement - or P - selectin - defi cient mice showed marked improvement
in the survival of refrigerated platelets. Removal of GPIb
' s N - terminal ligand
binding - domain using the
O
-sialoglycoprotein endopeptidase restored the circula-
tion of refrigerated murine wild-type platelets, indicating that the external domain
of GPIb
α
initiates clearance [8]. Subsequent work narrowed carbohydrate recogni-
tion by integrin
α
glycans
(Figure 29.4) [9, 10]. While resting platelets weakly bind sWGA, refrigerated plate-
lets have markedly increased binding, suggesting that altered epitope presentation
and/or clustering of exposed
α
M
β
2
to exposed
β
GlcNAc residues on
N
- linked GPIb
α
can facilitate lectin binding to
refrigerated platelets, representing another example for a physiologic modulation
of lectin binding and for sugar-encoded information (for further examples, please
see Chapters 19 , 25 and 27) (Figure 29.4). What causes these alterations of specifi c
carbohydrate epitopes on platelet glycoproteins during refrigeration? Actin rear-
rangement during refrigeration is likely to initiate surface VWF receptor redistri-
bution from linear arrays into aggregates [8]. Platelet refrigeration can therefore
cause profound changes in the presentation of exposed glycans on the platelet
surface. Glycan clustering is detected early after refrigeration [8, 9], but may
increase with long-term platelet storage and refrigeration in plasma (Figure 29.4 ).
Integrin
β
GlcNAc on GPIb
α
3
, the most abundant platelet integrin with 80 000 copies per platelet,
also contains incomplete glycans with exposed
α
IIb
β
β
GlcNAc and/or Gal moieties [11] .
It remains to be determined if changes in the
α
IIb
β
3
integrin and its glycans occur
during platelet refrigeration.
A potential method for preventing the rapid clearance of refrigerated platelets
for transfusion was envisioned to be enzymatic galactosylation of surface
β
GlcNAc
residues on platelet glycoproteins using a
β
1 - 4 - galactosyltransferase (
β
4GalT ).
Figure 29.4
Proposed mechanisms for cold -
induced platelet clearance. The VWF receptor
complex, specifi cally GPIb
sis of short-term refrigerated platelets. Extended
refrigeration may be followed by additional sur-
face changes such as 'hyperclustering' of recep-
tors and their associated glycans and/or carbo-
hydrate residues, leading to recognition and
phagocytosis by
, has complete and
α
incomplete
N
- linked
glycans
with
exposed
GlcNAc and/or Gal residues. Clustering of
VWF receptors and of exposed
β
GlcNAc initi-
ates recognition and phagocytosis by the mac-
rophage
2
integrin - independent
mechanisms, probably through galactose rece-
ptors and/or scavenger receptors.
M
β
α
β
M
2
integrin. Coverage of exposed
α
β
GlcNAc residues by Gal prevents phagocyto-
β
