Date Published: March 14, 2012
Publisher: Hindawi Publishing Corporation
Author(s): Rukmini Govekar, Poonam Kawle, Renjan Thomas, Suresh Advani, Sheena PV, Surekha Zingde.
In pathological conditions with concurrent neutrophilia, modifications of erythrocyte membrane proteins are reported. In chronic myeloid leukemia (CML), a myeloproliferative disease wherein neutrophilia is accompanied by enhanced erythrophagocytosis, we report for the first time excessive cleavage of erythrocyte band 3. Distinct fragments of band 3 serve as senescent cell antigens leading to erythrophagocytosis. Using immunoproteomics, we report the identification of immunogenic 43 kDa fragment of band 3 in 68% of CML samples compared to their detection in only 38% of healthy individuals. Thus, excessive fragmentation of band 3 in CML, detected in our study, corroborated with the eryptotic phenotype. We demonstrate the role of neutrophilic cathepsin G, detected as an immunogen on erythrocyte membrane, in band 3 cleavage. Cathepsin G from serum adsorbs to the erythrocyte membrane to mediate cleavage of band 3 and therefore contribute to the eryptotic phenotype in CML.
Neutrophils are inflammatory cells which contribute to tissue repair. Antithetically, neutrophilia and associated effects of the neutrophilic proteases and oxidases can lead to additional pathology at the site of inflammation . In patients with cardiovascular disease , ischemic stroke , and in pregnancy , neutrophilia co-occurs with modifications of erythrocyte membrane protein band 3, which is either aggregated or cleaved. The modified band 3 is a senescent cell antigen, which can mediate immune recognition and erythrophagocytosis [5, 6].
Thus, co-occurrence of extensively cleaved band 3 and adherent cathepsin G on the membranes of CML erythrocytes, along with the in vitro demonstration of the role of cathepsin G in proteolysis of band 3, indicates involvement of cathepsin G in band 3 cleavage in vivo. Moreover, the excessive cleavage of band 3 in CML correlates with greater detection of immunogenic fragments of band 3, indicative of eryptotic phenotype. Thus, cathepsin G-mediated proteolysis of band 3 could exemplify a mechanism for the generation of eryptotic phenotype in CML.