Monocyte FcyRs in HIT

Monocytes and macrophages possess several different classes of FcyR (Table 1), and thus may play a part in influencing the frequency and severity of both thrombocytopenia and thrombosis in HIT. One role, discussed in the previous section, involves their potential to influence the balance between platelet activation and reticuloendothelial-mediated platelet clearance in HIT. Another function recently proposed for monocytes is that of contributing to the procoagulant state in HIT (a role posited previously for endothelial cells) (see Chapter 9). Pouplard and colleagues (2001) found that by adding HIT-IgG and PF4 (or PF4-H) directly to isolated monocytes or to whole blood, the monocytes produced TF, an effect that could be inhibited by high concentrations of heparin. Arepally and Mayer (2001) found that monocytes expressed surface TF when incubated with PF4 in the presence of either HIT-IgG or the HIT-mimicking murine monoclonal antibody, KKO. Because monocytes express sulfated proteoglycans on their surface, PF4 binding to monocytes can occur in the absence of added heparin. These studies raise the possibility that monocytes play an important role in the pathogenesis of the procoagulant state characteristic of HIT. Animal models suggest there may be a balance between platelet activation by HIT-IgG (predisposing one to thrombosis) and clearance of platelets by monocytes-macrophages (protecting somewhat against thrombosis). However, phagocytosis or NK cell destruction of antibody-sensitized platelets likely contribute to the thrombocytopenia since HIT is associated with an overrepresentation of FcyRIIIa-Val158 (Gruel et al., 2004), an FcyR with higher affinity for IgG1 and IgG3 (Table 1).

0 0

Post a comment