Human monocytes subjected to ischaemia/reperfusion inhibit angiogenesis and wound healing in vitro

受到缺血/再灌注的人类单核细胞在体外抑制血管生成和伤口愈合

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作者:Lars Hummitzsch, Martin Albrecht, Karina Zitta, Katharina Hess, Kerstin Parczany, René Rusch, Jochen Cremer, Markus Steinfath, Assad Haneya, Fred Faendrich, Rouven Berndt

Conclusion

In summary, monocytes showed no significant change in cellular integrity and monocyte subtype after I/R. Functionally, monocytes might have a rather detrimental influence during the initial phase of I/R, suppressing endothelial cell migration and neoangiogenesis.

Methods

To clarify the role of classical monocytes in I/R injury, isolated human monocytes were subjected to I/R in vitro (3 hours ischaemia followed by 24 hours of reperfusion). Cellular resilience, monocyte differentiation, cytokine secretion, as well as influence on endothelial tube formation, migration and cell recovery were investigated.

Results

We show that I/R supported an enhanced resilience of monocytes and induced intracellular phosphorylation of the prosurvival molecules Erk1/2 and Akt. FACS analysis showed no major alteration in monocyte subtype differentiation and surface marker expression under I/R. Further, our experiments revealed that I/R changes the cytokine secretion pattern, release of angiogenesis associated proteins and MMP-9 activity in supernatants of monocytes exposed to I/R. Supernatants from monocytes subjected to I/R attenuated endothelial tube formation as indicator for angiogenesis as well as endothelial cell migration and recovery.

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