Platelet activation and inhibition of malarial cytoadherence by the anti-CD36 IgM monoclonal antibody NL07.
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.
Alessio
M
M
Dipartimento di Genetica, Biologia e Chimica Medica, Università di Torino, Italy.
Greco
N J
NJ
Primo
L
L
Ghigo
D
D
Bosia
A
A
Tandon
N N
NN
Ockenhouse
C F
CF
Jamieson
G A
GA
Malavasi
F
F
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology*; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D018955:CD36 Antigens; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D004912:Erythrocytes / Q000187:drug effects / Q000502:physiology*; D005434:Flow Cytometry; D006681:HLA-D Antigens / Q000096:biosynthesis; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D006801:Humans; D007075:Immunoglobulin M / Q000494:pharmacology*; D007700:Kinetics; D016778:Malaria, Falciparum / Q000097:blood*; D008545:Melanoma; D010963:Plasmodium falciparum; D015539:Platelet Activation; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010980:Platelet Membrane Glycoproteins / Q000276:immunology / Q000502:physiology*; D013915:Thrombasthenia / Q000097:blood; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018955:CD36 Antigens; D006681:HLA-D Antigens; D015395:Histocompatibility Antigens Class I; D007075:Immunoglobulin M; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; C022571:adenosine 5'-O-(3-thiotriphosphate); D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate