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Article

Plasticity of High-Density Neutrophils in Multiple Myeloma is Associated with Increased Autophagy Via STAT3

1
Department of Surgery and Medical Specialties, University of Catania, 95123 Catania, Italy
2
Division of Hematology, Azienda Ospedaliera Policlinico e Vittorio Emanuele di Catania, 95123 Catania, Italy
3
Department of Medical, Surgical Sciences and Advanced Technologies “G. F. Ingrassia”, University of Catania, 95123 Catania, Italy
4
CNR-IMM, Ottava Strada n.5, 95121 Catania, Italy
5
Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
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Department of Biological, Geological and Environmental Science, University of Catania, 95124 Catania, Italy
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(14), 3548; https://doi.org/10.3390/ijms20143548
Received: 6 June 2019 / Revised: 13 July 2019 / Accepted: 16 July 2019 / Published: 19 July 2019
In both monoclonal gammopathy of uncertain significance (MGUS) and multiple myeloma (MM) patients, immune functions are variably impaired, and there is a high risk of bacterial infections. Neutrophils are the most abundant circulating leukocytes and constitute the first line of host defense. Since little is known about the contribution of autophagy in the neutrophil function of MGUS and MM patients, we investigated the basal autophagy flux in freshly sorted neutrophils of patients and tested the plastic response of healthy neutrophils to soluble factors of MM. In freshly sorted high-density neutrophils obtained from patients with MGUS and MM or healthy subjects, we found a progressive autophagy trigger associated with soluble factors circulating in both peripheral blood and bone marrow, associated with increased IFNγ and pSTAT3S727. In normal high-density neutrophils, the formation of acidic vesicular organelles, a morphological characteristic of autophagy, could be induced after exposure for three hours with myeloma conditioned media or MM sera, an effect associated with increased phosphorylation of STAT3-pS727 and reverted by treatment with pan-JAK2 inhibitor ruxolitinib. Taken together, our data suggest that soluble factors in MM can trigger contemporary JAK2 signaling and autophagy in neutrophils, targetable with ruxolitinib. View Full-Text
Keywords: neutrophil; autophagy; IFN-γ; STAT-3; ruxolitinib neutrophil; autophagy; IFN-γ; STAT-3; ruxolitinib
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MDPI and ACS Style

Puglisi, F.; Parrinello, N.L.; Giallongo, C.; Cambria, D.; Camiolo, G.; Bellofiore, C.; Conticello, C.; Del Fabro, V.; Leotta, V.; Markovic, U.; Sapienza, G.; Barbato, A.; Scalese, S.; Tibullo, D.; Brundo, M.V.; Palumbo, G.A.; Di Raimondo, F.; Romano, A. Plasticity of High-Density Neutrophils in Multiple Myeloma is Associated with Increased Autophagy Via STAT3. Int. J. Mol. Sci. 2019, 20, 3548. https://doi.org/10.3390/ijms20143548

AMA Style

Puglisi F, Parrinello NL, Giallongo C, Cambria D, Camiolo G, Bellofiore C, Conticello C, Del Fabro V, Leotta V, Markovic U, Sapienza G, Barbato A, Scalese S, Tibullo D, Brundo MV, Palumbo GA, Di Raimondo F, Romano A. Plasticity of High-Density Neutrophils in Multiple Myeloma is Associated with Increased Autophagy Via STAT3. International Journal of Molecular Sciences. 2019; 20(14):3548. https://doi.org/10.3390/ijms20143548

Chicago/Turabian Style

Puglisi, Fabrizio, Nunziatina L. Parrinello, Cesarina Giallongo, Daniela Cambria, Giuseppina Camiolo, Claudia Bellofiore, Concetta Conticello, Vittorio Del Fabro, Valerio Leotta, Uros Markovic, Giuseppe Sapienza, Alessandro Barbato, Silvia Scalese, Daniele Tibullo, Maria V. Brundo, Giuseppe A. Palumbo, Francesco Di Raimondo, and Alessandra Romano. 2019. "Plasticity of High-Density Neutrophils in Multiple Myeloma is Associated with Increased Autophagy Via STAT3" International Journal of Molecular Sciences 20, no. 14: 3548. https://doi.org/10.3390/ijms20143548

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