The production of interleukin-8 (IL-8) by malignant megakaryocytes appears to promote emperipolesis between neutrophils and megakaryocytes, which contributes to developing a tumor growth factor beta (TGF-β) microenvironment that favors fibrosis, it could play a role in myelofibrosis, according to a recently published study in Experimental Hematology.
Emperipolesis, the passage of 1 cell type into the cytoplasm of another without any of them suffering structural damage, is particularly frequent in megakaryocytes under stress conditions, the researchers noted. Two studies have already demonstrated emperipolesis between megakaryocytes and neutrophils occurs in myelofibrosis and leads to the release of neutrophil granules that, in turn, leads to cell apoptosis and the production of TGF-β, they added.
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“Although the pathobiological relevance of emperipolesis in the development of myelofibrosis is now well recognized, studies on the mechanisms that drive this process in myelofibrosis are scanty,” the authors wrote.
The production of IL-8 has been associated with the pathogenesis of fibrosis in a previous study by the authors; however, the mechanism explaining its role in the process remained unclear. Therefore the authors designed an animal model experiment to study the underlying processes.
The experiment was based on the rationale that CXCL1 is the murine equivalent of IL-8, as they both have neutrophil chemotactic properties. Researchers treated experimental mice with the CXCL1 inhibitor reparixin and then observed its effect on neutrophil and megakaryocyte emperipolesis on electron microscopy.
The authors observed that the administration of reparixin in myelofibrotic mice significantly reduced the emperipolesis between neutrophils and megakaryocytes. Although the number of megakaryocytes remained unaffected, the neutrophil count was greatly reduced.
“This link provides a rationale to explain why greater levels of IL-8 represent a biomarker for adverse disease progression: in other words, greater IL-8, greater emperipolesis, and TGF-β release in the microenvironment and higher levels of fibrosis,” the authors wrote.
The findings of these studies, together with those in previous studies, encouraged the authors to recommend IL-8 as a biomarker for levels of fibrosis in myelofibrosis.
Arciprete F, Verachi P, Martelli F, et al. Inhibition of CXCR1/2 reduces the emperipolesis between neutrophils and megakaryocytes in the GATA1 model of myelofibrosis. Exp Hematol. Published online February 23, 2023. doi:10.1016/j.exphem.2023.02.003