Hypoxia directed migration of human naïve monocytes is associated with an attenuation of cytokine release: indications for a key role of CCL26.

Numerous tissue-derived factors have been postulated to be involved in tissue migration of circulating monocytes. The aim of this study was to evaluate whether a defined hypoxic gradient can induce directed migration of naïve human monocytes and to identify responsible autocrine/paracrine factors. Monocytes were isolated from peripheral blood mononuclear cells, transferred into chemotaxis chambers and subjected to a defined oxygen gradient with or without the addition of CCL26. Cell migration was recorded and secretome analyses were performed. Cell migration recordings revealed directed migration of monocytes towards the source of hypoxia. Analysis of the monocyte secretome demonstrated a reduced secretion of 70% (19/27) of the analyzed cytokines under hypoxic conditions. The most down-regulated factors were CCL26 (- 99%), CCL1 (- 95%), CX3CL1 (- 95%), CCL17 (- 85%) and XCL1 (- 83%). Administration of recombinant CCL26 abolished the hypoxia-induced directed migration of human monocytes, while the addition of CCL26 under normoxic conditions resulted in a repulsion of monocytes from the source of CCL26. Hypoxia induces directed migration of human monocytes in-vitro. Autocrine/paracrine released CCL26 is involved in the hypoxia-mediated monocyte migration and may represent a target molecule for the modulation of monocyte migration in-vivo.

Citation

Lars Hummitzsch, Rouven Berndt, Matthias Kott, Rene Rusch, Fred Faendrich, Matthias Gruenewald, Markus Steinfath, Martin Albrecht, Karina Zitta. Hypoxia directed migration of human naïve monocytes is associated with an attenuation of cytokine release: indications for a key role of CCL26. Journal of translational medicine. 2020 Oct 21;18(1):404

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PMID: 33087148

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