FcγRIIa Ligation Induces Platelet Hypersensitivity to Thrombotic Stimuli

Abstract

Platelets are known for their important role in hemostasis, however their significance in other functions, including inflammation and infection, are becoming more apparent. Patients with systemic lupus erythematosus (SLE) are known to have circulating IgG complexes in their blood and are highly susceptible to thrombotic events. Because platelets express a single receptor for IgG, we tested the hypothesis that ligation of this receptor (FcγRIIa) induces platelet hypersensitivity to thrombotic stimuli. Platelets from SLE patients were considerably more sensitive to thrombin compared to healthy volunteers, and this correlated with elevated levels of surface IgG on SLE platelets. To test whether FcγRIIa ligation stimulated thrombin hypersensitivity, platelets from healthy volunteers were incubated with buffer or heat-aggregated IgG, then stimulated with increasing concentrations of thrombin. Interestingly, heat-aggregated IgG-stimulated platelets, but not buffer-treated platelets, were hypersensitive to thrombin, and hypersensitivity was blocked by an anti-FcγRIIa monoclonal antibody (mAb). Thrombin hypersensitivity was not due to changes in thrombin receptor expression (GPIbα or PAR1) but is dependent on activation of shared signaling molecules. These observations suggest that ligation of platelet FcγRIIa by IgG complexes induces a hypersensitive state whereby small changes in thrombotic stimuli may result in platelet activation and subsequent vascular complications such as transient ischemic attacks or stroke.

Characterization of a transgenic mouse model of chronic conditional platelet depletion

“…After labeling, platelets were washed once at 1900 g for 10 minutes to remove excess antibody. Platelets were then resuspended and counted in pH 7.4 experimental buffer (8.0 g/L sodium chloride, 0.2 g/L potassium chloride, 0.2 g/L magnesium chloride, 0.45 g/L sodium phosphate dibasic, 0.9 g/L HEPES, 3.5 g/L bovine serum albumin, 1.0 g/L dextrose, pH adjusted to 7.4). Platelet counts were adjusted to a concentration of 2 × 10 9 /mL.…”

Platelet impedance adhesiometry: A novel technique for the measurement of platelet adhesion and spreading

“…To further analyze the suitability of impedimetry for measuring platelet adhesion and spreading, we investigated in vivo parameters that could potentially affect platelet adhesion. Increased platelet activity and reactivity in acute and chronic allergic or other hyperimmune states are well documented . Impedimetric measurement detected similar, increased platelet adhesion in individuals with a history of allergic diseases.…”

Antimicrobial and antiviral effects of human defensins: pathogenetic value and prospective application to medicinal therapy

“…Действительно, вакуоль, содержащая патогены, имеет возможность слия-ния с альфа-гранулами, в которых содержится мно-го микробоцидных молекул [198]. Кроме того, было установлено, что бактерии могут быть уничтожены тромбоцитами при интернализации, опосредован-ной FcγRII, при условии, что бактерии были внача-ле опсонизированы иммуноглобулином [33]. Таким образом, судьба бактерий, захваченных тромбо-цитами, остается предметом обсуждения, т. е. это либо средство защиты, либо механизм укрытия для бактерий.…”