Abstract
Phagocytes were first described 120 years ago. Although the molecular mechanisms involved in initiating phagocytosis (through Fc or other receptors) are still not fully understood, the roles of phagocytes in innate and adaptive immunity have been well studied. Phagocytes in the reticuloendothelial system, particularly macrophages, have been implicated in the clearance of senescent blood cells. The destruction of these cells may be primarily mediated through an Fcindependent pathway. Fc-independent phagocytosis may also play an important role in platelet clearance, including immune thrombocytopenia (ITP). The two major platelet antigens targeted in ITP are GPIIbIIIa and the GPIb complex. It has been demonstrated that anti-GPIbα antibodies, in contrast to anti-GPIIbIIIa, can induce thrombocytopenia in an Fcindependent manner. We further demonstrated in an animal model that intravenous IgG is not able to ameliorate thrombocytopenia caused by most anti-GPIbα antibodies, though it is effective in anti-GPIIbIIIa mediated thrombocytopenia. Our data was supported by a recent retrospective study of ITP patients. Therefore, identification of antibody specificity (e.g. anti-GPIIbIIIa (Fc-dependent) versus anti-GPIbα (Fc-independent)) in patients may be important for ITP therapy.
Keywords: Platelets, thrombocytopenia, intravenous IgG, phagocytosis, thrombosis
Cardiovascular & Hematological Disorders-Drug Targets
Title: Fc-Independent Phagocytosis: Implications for Intravenous IgG Therapy in Immune Thrombocytopenia
Volume: 8 Issue: 4
Author(s): Michelle Lee Webster, Guangheng Zhu, Yan Li and Heyu Ni
Affiliation:
Keywords: Platelets, thrombocytopenia, intravenous IgG, phagocytosis, thrombosis
Abstract: Phagocytes were first described 120 years ago. Although the molecular mechanisms involved in initiating phagocytosis (through Fc or other receptors) are still not fully understood, the roles of phagocytes in innate and adaptive immunity have been well studied. Phagocytes in the reticuloendothelial system, particularly macrophages, have been implicated in the clearance of senescent blood cells. The destruction of these cells may be primarily mediated through an Fcindependent pathway. Fc-independent phagocytosis may also play an important role in platelet clearance, including immune thrombocytopenia (ITP). The two major platelet antigens targeted in ITP are GPIIbIIIa and the GPIb complex. It has been demonstrated that anti-GPIbα antibodies, in contrast to anti-GPIIbIIIa, can induce thrombocytopenia in an Fcindependent manner. We further demonstrated in an animal model that intravenous IgG is not able to ameliorate thrombocytopenia caused by most anti-GPIbα antibodies, though it is effective in anti-GPIIbIIIa mediated thrombocytopenia. Our data was supported by a recent retrospective study of ITP patients. Therefore, identification of antibody specificity (e.g. anti-GPIIbIIIa (Fc-dependent) versus anti-GPIbα (Fc-independent)) in patients may be important for ITP therapy.
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Cite this article as:
Webster Lee Michelle, Zhu Guangheng, Li Yan and Ni Heyu, Fc-Independent Phagocytosis: Implications for Intravenous IgG Therapy in Immune Thrombocytopenia, Cardiovascular & Hematological Disorders-Drug Targets 2008; 8 (4) . https://dx.doi.org/10.2174/187152908786786223
DOI https://dx.doi.org/10.2174/187152908786786223 |
Print ISSN 1871-529X |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-4063 |
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