DDAVP enhances the ability of blood monocytes to form rosettes with activated platelets by increasing the expression of P-selectin sialylated ligands on the monocyte surface.
The mechanism through which DDAVP (1-deamino-8-d-arginine vasopressin) promotes blood coagulation is not completely understood. As blood monocytes have been identified as a target for DDAVP, we investigated whether this drug increased monocyte adhesion to activated platelets, which would result in the close intercellular contact that is necessary for a juxtacrine effect on platelets and/or endothelium at sites of vascular injury. Monolayers of non-confluent monocytes adhered to glass slides were incubated with thrombin-activated, formaldehyde-fixed platelets before and after the adherent monocytes were stimulated with DDAVP or n-formyl-methyl-leucyl-phenylalanine (fMLP). The number of platelets involved in rosettes with monocytes was quantified, and the effect of DDAVP or fMLP on the monocyte surface expression of P-selectin ligands and CD11b/CD18 was assessed. DDAVP or fMLP increased the number of activated platelets involved in rosettes with monocytes by 2.8- and 4.9-fold respectively. EDTA and inhibitors of the P-selectin/counter-receptor interaction decreased the platelet numbers in rosettes by 80-90%, whereas inhibitors of the integrin-mediated adhesion reduced rosettes by 40-50%. Blocking the P-selectin glycoprotein ligand-1 (PSGL-1) with the monoclonal antibody, Pl-1, decreased the platelet numbers in rosettes by only 50%. In contrast, surface expression of the sialylated ligands of P-selectin and, to a lesser extent, of CD11b/CD18 increased upon monocyte activation with DDAVP or fMLP, whereas it decreased slightly with PSGL-1. These results indicate that DDAVP enhanced the ability of blood monocytes to bind activated platelets, mainly by increasing the expression of P-selectin sialylated ligands on the monocyte surface. A similar effect was achieved with fMLP.
Pereira
Arturo
A
Service of Haemotherapy, Haemostasis, and the Blood Bank, Hospital Clinic, Barcelona, Spain. apereira@clinic.ub.es
del Valle Onorato
María
M
Sanz
Cristina
C
D001792:Blood Platelets / Q000187:drug effects*; D018845:CD11 Antigens / Q000378:metabolism; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D019007:P-Selectin / Q000378:metabolism*; D015539:Platelet Activation; D012397:Rosette Formation
D018845:CD11 Antigens; D019007:P-Selectin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D003894:Deamino Arginine Vasopressin