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The Role of Zinc in GM‐CSF‐Induced Signaling in Human Polymorphonuclear Leukocytes
Author(s) -
van der Laan Marijke,
Büttgenbach Anna,
Wolf Jana,
Rink Lothar,
Wessels Inga
Publication year - 2022
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.202101106
Subject(s) - mapk/erk pathway , signal transduction , granulocyte colony stimulating factor receptor , zinc , phosphorylation , granulocyte macrophage colony stimulating factor , biology , granulocyte , kinase , microbiology and biotechnology , receptor , chemistry , cytokine , immunology , haematopoiesis , biochemistry , stem cell , organic chemistry
Scope Zinc is suggested to be necessary for functional signaling induced by certain growth factors. The granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) is a key factor for differentiation and activation of myeloid cells. This report analyses the impact of different zinc concentrations on GM‐CSF‐induced signaling in mature polymorphonuclear leukocytes (PMN). Methods and results As measured by flow cytometry, zinc increases surface GM‐CSF receptor (GM‐CSFR) in PMN, whereas monocytes respond with decreased GM‐CSFR surface expression. Since total cellular GM‐CSFR expression remains unaffected, the observed zinc‐induced GM‐CSFR surface dynamics may be explained by receptor redistribution. In PMN, zinc enhanced phosphorylation of mitogen‐activated protein kinases (MAPK) in a dose‐dependent manner as found in western blot. Zinc‐induced MAPK phosphorylation is additionally augmented by moderate GM‐CSF stimulation. Conclusion The present study demonstrates the opposing influence of zinc on GM‐CSFR surface expression in monocytes and PMN. Zinc and GM‐CSF, use in optimized concentrations, augment MAPK signaling, and increase expression of MAPK‐induced myeloid cell leukemia‐1 (Mcl‐1) in PMN. Thus, this study concludes that zinc strengthens growth factor‐induced signaling. Hence, the study provides a basis for further in vivo studies, focusing on the therapeutic value of zinc in patients with a disturbed GM‐CSF signaling.