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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Impairment of G-CSF receptor on granulocytic progenitor cells causes neutropenia in protein malnutrition

Full text
Author(s):
Aparecida Hastreiter, Araceli [1] ; Makiyama, Edson Naoto [1] ; Borelli, Primavera [1] ; Fock, Ricardo Ambrosio [1]
Total Authors: 4
Affiliation:
[1] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, Sao Paulo, SP - Brazil
Total Affiliations: 1
Document type: Journal article
Source: NUTRITION; v. 69, JAN 2020.
Web of Science Citations: 0
Abstract

Objective: It is well known that protein malnutrition (PM) states can affect hematopoiesis, leading to severe leukopenia and reduced number of granulocytes, which act as the first line of defense, and are important to the innate immune response. The aim of this study was to elucidate some of the mechanisms involved in the impairment of granulopoiesis in PM. Methods: Male C57BL/6 mice were submitted to PM with a low-protein diet containing 2% protein. Control mice were fed a 12% protein-containing diet. Bone marrow histology and the percentage of granulocytic progenitors were evaluated after in vivo granulocyte-colony stimulating factor (G-CSF) stimulus. Cell proliferation, STAT3 signaling, and the expression of G-CSF receptor were evaluated in hematopoietic progenitor cells. Results: Malnourished animals presented with leukopenia associated with reduced number of granulocytes and reduced percentage of granulocytic progenitors; however, no differences were observed in the regulatory granulopoietic cytokine G-CSF. Additionally, the malnourished group presented with impaired response to in vivo G-CSF stimulus compared with control animals. PM was implicated in decreased ability of c-Kit(+) cells to differentiate into myeloid progenitor cells and downregulated STAT3 signaling. Furthermore, the malnourished group exhibited reduced expression of G-CSF receptor on granule-monocytic progenitors. This reduced expression was not completely reversible with G-CSF treatment. Conclusions: This study implies that PM promotes intrinsic alterations to hematopoietic precursors, which result in hematologic changes, mainly neutropenia, observed in peripheral blood in PM states. (C) 2019 Elsevier Inc. All rights reserved. (AU)

FAPESP's process: 18/25813-8 - Effect of protein malnutrition on hematopoiesis. marrow endothelial cell involvement and action of granulocytic colony stimulating factor (G-CSF)
Grantee:Ricardo Ambrósio Fock
Support Opportunities: Regular Research Grants