Complement-mediated granulocyte dysfunction in paroxysmal nocturnal
hemoglobinuria
PR Craddock, J Fehr and HS Jacob
In paroxysmal nocturnal hemoglobinuria (PNH), infection, both viral and
bacterial, disproportionate to the mild neutropenia seen in many such
patients is responsible for significant morbidity. We report impaired
granulocyte chemotaxis efficiency which may contribute to the problems
induced by bacterial infections. PNH (but not normal) granulocytes, after
exposure to very small concentrations of activated serum complement
components, migrate poorly, as documented by their inhibited chemotaxis
toward bacterial products or activated complement components in Boyden
chambers. The granulocytes remain intact, excluding trypan blue,
phagocytosing, and killing bacteria, despite this activated complement
exposure. It is also suggested that this chemotactic defect may involve
only a clone of cells, analogous to the clonal lysis of PNH erythrocytes;
those few granulocytes capable of migration after exposure to activated
complement contain normal quantities of leukocyte alkaline phosphatase
(LAP), in contrast to the LAP deficiency of the overall PNH granulocyte
population. Since bacterial infection may initiate or potentiate hemolysis,
one of the major symptoms of the disease, these results could explain much
of the morbidity of PNH.
Volume 47,
Issue 6,
pp. 931-939,
06/01/1976
Copyright © 1976 by The American Society of Hematology
