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Incomplete antigenic cross-reactivity between platelets and megakaryocytes:
relevance to ITP
CP Stahl, D Zucker-Franklin and TP McDonald
Immune thrombocytopenias are usually associated with normal or increased
numbers of megakaryocytes in the marrow. Therefore, the mechanism(s)
responsible for the destruction of circulating platelets may not affect
megakaryocytes in the same way. One of the possibilities which could
account for the differential effect on the cells would be the development
of antibodies to components of platelet membranes which are not exposed on
the surface of all megakaryocytes. To investigate this possibility, a
rabbit antiserum specific for mouse platelets was tested against fresh and
cultured mouse megakaryocytes by indirect immunofluorescence. This
antiserum cross-reacted with 46% of fresh murine megakaryocytes and 54% of
cultured megakaryocytes. Phase- contrast microscopy revealed the reacting
megakaryocytes to be fully granulated with irregular contours and in the
process of releasing platelets. Nonreactive megakaryocytes demonstrated
smooth contours and lacked morphological evidence of thrombocytopoiesis.
Electron microscopy showed that only in megakaryocytes (MK) with an
irregular contour had the demarcation membrane system (DMS) reached
continuity with the plasma membrane. Ultrastructural analysis of
megakaryocytes from patients with ITP showed approximately 25% to 50% of
megakaryocytes without evidence of injury, whereas 50% to 75% had extensive
damage. In undamaged cells, platelet territories had not yet reached the
peripheral zone. The DMS of damaged megakaryocytes opened to the exterior
elaborating platelets. The observations suggested that some platelet
antibodies react only with megakaryocytes which have reached the stage of
thrombocytopoiesis. Relevant target antigens may not be exposed on all
megakaryocytes before cytoplasmic fragmentation occurs.
Volume 67,
Issue 2,
pp. 421-428,
02/01/1986
Copyright © 1986 by The American Society of Hematology
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