The influence of protein malnutrition on the production of GM-CSF and M-CSF by macrophages

Dalila Cunha De Oliveira,Araceli Aparecida Hastreiter,Primavera Borelli,Ricardo Ambrósio Fock

doi:10.1590/s1984-82502016000300003

Abstract

It is well established that protein malnutrition (PM) impairs immune defenses and increases susceptibility to infection. Macrophages are cells that play a central role in innate immunity, constituting one of the first barriers against infections. Macrophages produce several soluble factors, including cytokines and growth factors, important to the immune response. Among those growth factors, granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF). GM-CSF and M-CSF are important to monocyte and macrophage development and stimulation of the immune response process. Knowing the importance of GM-CSF and M-CSF, we sought to investigate the influence of PM on macrophage production of these growth factors. Two-month-old male BALB/c mice were subjected to PM with a low-protein diet (2%) and compared to a control diet (12%) mouse group. Nutritional status, hemogram and the number of peritoneal cells were evaluated. Additionally, peritoneal macrophages were cultured and the production of GM-CSF and M-CSF and mRNA expression were evaluated. To determine if PM altered macrophage production of GM-CSF and M-CSF, they were stimulated with TNF-α. The PM animals had anemia, leukopenia and a reduced number of peritoneal cells. The production of M-CSF was not different between groups; however, cells from PM animals, stimulated with or without TNF-α, presented reduced capability to produce GM-CSF. These data imply that PM interferes with the production of GM-CSF, and consequently would affect the production and maturation of hematopoietic cells and the immune response.

Highlights

Protein malnutrition (PM) is the most widespread nutritional disorder in developing countries and it is associated with high rates of morbidity and mortality
The results showed that the level of granulocytemacrophage colony-stimulating factor (GM-CSF) was diminished in the PM group without TNF-α stimulation when compared with the control group level (Figure 2B)
We evaluated the capacity of macrophages to produce GM-CSF and macrophage colony-stimulating factor (M-CSF) in a PM model

Summary

Introduction

Protein malnutrition (PM) is the most widespread nutritional disorder in developing countries and it is associated with high rates of morbidity and mortality. PM decreases immune defenses, increasing susceptibility to infection. Though all forms of immune response can be affected by PM, non-specific defense and cell-mediated immunity are the most severely affected (Keusch, 2003; Calder, 2013). The term “cell-mediated immunity” refers to the recognition and/or killing of pathogens by phagocytes, cytotoxic T-lymphocytes and cytokines. Monocytes and macrophages are critical effectors of cell-mediated immunity and regulate cells of the innate and adaptive. GM-CSF and M-CSF mediate cell survival, proliferation and differentiation and modulate chemotaxis, degranulation, activation, adhesion, cytotoxicity and mRNA phenotype changes of various blood cell populations (Barreda, 2004; Hamilton, Achuthan, 2013). M-CSF is detectable in the steady state, but GM-CSF requires an inflammatory stimulation (IL-1, TNF-α or LPS) to reach measurable levels (Hamilton, 2008; Sierra-Filardi et al, 2014)

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Conclusion