Chemistry Reference
In-Depth Information
29
Platelet Glycoproteins as Lectins in Hematology
Karin Hoffmeister and Herv é Falet
In response to hemorrhage, circulating platelets roll on the exposed subendothe-
lium, adhere and form aggregates to seal a vascular leak. These processes involve
platelet receptors such as von Willebrand factor (VWF) receptor complex, selectins
and integrins. Platelet glycans have been investigated mainly in relation to platelet
survival. Specifi cally, platelets exposed to temperatures below 37 ° C are rapidly
cleared by hepatic lectins and clustered platelet surface glycoproteins - a phenom-
enon that prohibits platelet refrigeration. Transfusion of human platelets, stored
in blood banks as concentrates, remains the treatment of choice for throm-
bocytopenia and bleeding. However, platelets must be stored at room temperature,
leading to major problems such as viral and bacterial growth, the loss of platelet
functionality, and the complexity of managing supply with demand. A better
understanding of the factors that mediate platelet clearance may lead to improved
platelet storage. This chapter focuses on platelet adhesive receptors such as glyco-
protein (GP)Ib and P-selectin (for illustration of the lectin site of P- selectin, please
see Figure 16.1h; for its domain structure, see Figure 19.1; for its role in infl am-
mation, see Chapter 27.4) and the P - selectin glycoprotein ligand ( PSGL ) - 1. These
glycoproteins interact with lectins or 'act' as lectins
in vitro
and
in vivo
(for defi ni-
tion of the term 'lectin', please see Chapter 15 ).
29.1
Platelet Physiology
Human platelets are anuclear discoid cell fragments that measure 2-4
μ
m in
diameter. They circulate in the bloodstream at a concentration of 150- 400
l
with a half-life of 8-10 days. Platelets are formed by megakaryocytes in the bone
marrow, and are eliminated primarily by the spleen and the liver. Platelets play
an essential role in hemostasis and coagulation. Platelet dysfunction or low blood
count predisposes to hemorrhage, while their hyperactivation increases the risk
of thrombosis [1]. Once activated, platelets change shape and secrete their granular
contents (Figure 29.1). Platelet adhesion, activation and aggregation are mediated
×
10
3
/
μ
