Hydroxyethyl Starch 130/0.4 Binds to Neutrophils Impairing Their Chemotaxis through a Mac-1 Dependent Interaction.

Alessandro Trentini, Francesca Murganti, Valentina Rosta, Carlo Cervellati, Maria Cristina Manfrinato, Savino Spadaro, Franco Dallocchio, Carlo Alberto Volta, Tiziana Bellini

Journal: International journal of molecular sciences 2019;20(4):817

PMID: 30769810

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Abstract

Several studies showed that hydroxyethyl starch (HES), a synthetic colloid used in volume replacement therapies, interferes with leukocyte-endothelium interactions. Although still unclear, the mechanism seems to involve the inhibition of neutrophils' integrin. With the aim to provide direct evidence of the binding of HES to neutrophils and to investigate the influence of HES on neutrophil chemotaxis, we isolated and treated the cells with different concentrations of fluorescein-conjugated HES (HES-FITC), with or without different stimuli (N-Formylmethionine-leucyl-phenylalanine, fMLP, or IL-8). HES internalization was evaluated by trypan blue quenching and ammonium chloride treatment. Chemotaxis was evaluated by under-agarose assay after pretreatment of the cells with HES or a balanced saline solution. The integrin interacting with HES was identified by using specific blocking antibodies. Our results showed that HES-FITC binds to the plasma membrane of neutrophils without being internalized. Additionally, the cell-associated fluorescence increased after stimulation of neutrophils with fMLP ( < 0.01) but not IL-8. HES treatment impaired the chemotaxis only towards fMLP, event mainly ascribed to the inhibition of CD-11b (Mac-1 integrin) activity. Therefore, the observed effect mediated by HES should be taken into account during volume replacement therapies. Thus, HES treatment could be advantageous in clinical conditions where a low activation/recruitment of neutrophils may be beneficial, but may be harmful when unimpaired immune functions are mandatory.

Address: Section of Medical Biochemistry, Molecular Biology and Genetics, Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, 44121 Ferrara, Italy. [email protected].; Section of Medical Biochemistry, Molecular Biology and Genetics, Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, 44121 Ferrara, Italy. [email protected].; Technische Universität Dresden, Research Center for Regenerative Therapies, 01307 Dresden, Germany. [email protected].; Section of Medical Biochemistry, Molecular Biology and Genetics, Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, 44121 Ferrara, Italy. [email protected].; Section of Medical Biochemistry, Molecular Biology and Genetics, Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, 44121 Ferrara, Italy. [email protected].; Section of Medical Biochemistry, Molecular Biology and Genetics, Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, 44121 Ferrara, Italy. [email protected].; Section of Anesthesia and Intensive Care, Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy. [email protected].; Section of Medical Biochemistry, Molecular Biology and Genetics, Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, 44121 Ferrara, Italy. [email protected].; Section of Anesthesia and Intensive Care, Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy. [email protected].; Section of Medical Biochemistry, Molecular Biology and Genetics, Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, 44121 Ferrara, Italy. [email protected].

DOI: 10.3390/ijms20040817

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https://antibodies.cancer.gov/detail/CPTC-ITGAM-1

MeSH Terms: Chemotaxis, Leukocyte, Fluorescein-5-isothiocyanate, Humans, Hydroxyethyl Starch Derivatives, Interleukin-8, Macrophage-1 Antigen, N-Formylmethionine Leucyl-Phenylalanine, Neutrophils