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Platelet activation and inhibition of malarial cytoadherence by the
anti-CD36 IgM monoclonal antibody NL07
M Alessio, NJ Greco, L Primo, D Ghigo, A Bosia, NN Tandon, CF Ockenhouse, GA Jamieson and F Malavasi
Dipartimento di Genetica, Biologia e Chimica Medica, Universita di Torino,
Italy.
The surface glycoprotein CD36 (GPIV) is known to mediate the adhesion of
Plasmodium falciparum malaria-infected red blood cells and to be a receptor
for extracellular matrix proteins such as collagen and thrombospondin. The
murine monoclonal IgM antibody NL07, which is specific for CD36, has now
been shown to also be a potent inhibitor of the adhesion of P falciparum
malaria-infected red blood cells to C32 melanoma cells. Treatment of
platelets with NL07 monoclonal antibody resulted in rapid degranulation,
release of ATP and serotonin, increase in [Ca2+]i, and tyrosine
phosphorylation of a substrate protein of 130 kD. In about one-half of the
experiments, activation with NL07 resulted in the formation of small
aggregates of 10 to 30 platelets, whereas in the other half of the
experiments, large aggregates were seen similar to those induced by
adenosine diphosphate (ADP) and these large aggregates could be converted
to the small aggregates by ATP alpha S or by AP-2 or other antibodies
against GPIIb and/or IIIa. Microaggregates of 2 to 5 platelets were seen
with Glanzmann's platelets that constitutively lack GPIIb/IIIa. Aggregate
formation was not seen with heat-treated serum, in the presence of anti C1q
antibodies, or when using C5-, C8-, or C9-deficient human sera. Although
activation of platelets with purified complement components results in a
slow morphologic change without aggregation, involvement of CD36 results in
rapid complement-mediated activation leading to formation of small
aggregates that is largely independent of GPIIb/IIIa and that, under
certain circumstances, proceeds to the formation of large ADP-dependent
aggregates.
Volume 82,
Issue 12,
pp. 3637-3647,
12/15/1993
Copyright © 1993 by The American Society of Hematology

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