Blood, 15 November 2001, Vol. 98, No. 10, pp. 3121-3127
RED CELLS
Deoxygenation of sickle cells stimulates Syk tyrosine kinase and
inhibits a membrane tyrosine phosphatase
Patrick Merciris,
Marie-Dominique Hardy-Dessources, and
Françoise Giraud
From the Biomembranes et Messagers Cellulaires,
Université Paris XI-Orsay, France; and Drépanocytose et
Pathologies de l'Endothélium, Pointe-à-Pitre, Guadeloupe,
France.
Polymerization of hemoglobin S in sickle red cells, in deoxygenated
conditions, is associated with K+ loss and cellular
dehydration. It was previously reported that deoxygenation of sickle
cells increases protein tyrosine kinase (PTK) activity and band 3 tyrosine phosphorylation and that PTK inhibitors reduce cell
dehydration. Here, the study investigates which PTKs are involved and
the mechanism of their activation. Deoxygenation of sickle cells
induced a 2-fold increase in Syk activity, measured by
autophosphorylation in immune complex assays, but had no effect on Lyn.
Syk was not stimulated by deoxygenation of normal red cells, and
stimulation was partly reversible on reoxygenation of sickle cells. Syk
activation was independent of the increase in intracellular
Ca++ and Mg2+ associated with
deoxygenation. Lectins that promote glycophorin or band 3 aggregation did not activate Syk. In parallel to Syk stimulation,
deoxygenation of sickle cells, but not of normal red cells, decreased
the activity of both membrane-associated protein tyrosine phosphatase
(PTPs) and membrane protein thiol content. In vitro pretreatment of Syk
immune complexes with membrane PTP inhibited Syk autophosphorylation.
It is suggested that Syk activation in vivo could be mediated by PTP
inhibition, itself resulting from thiol oxidation, as PTPs are known to
be inhibited by oxidants. Altogether these data indicate that Syk could
be involved in the mechanisms leading to sickle cell dehydration.
