Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock

In vitro and in vivo effects of human monocytes and their subsets on new vessel formation.

Abstract

Human monocytes (mo) can be divided into CD16- mo and CD16+ mo. Studies in mice suggested differential effects of mo subsets during new vessel formation. METHODS: The functional role of human mo subsets in neovascularization processes was investigated. For in vivo experiments, nude mice underwent unilateral hindlimb ischemia surgery before being injected with either total mo, CD16- mo or CD16+ mo isolated from healthy individuals. RESULTS: In vitro, cytokine array analysis demonstrated that mo release numerous angiogenic cytokines, some of which were differentially expressed in mo subsets. Sprout length was enhanced in endothelial cell spheroids being cultured in conditioned medium obtained from total mo and, to a lesser extent, also in supernatants of CD16- mo. Laser Doppler perfusion imaging up to day 28 after surgery revealed a trend towards improved revascularization in mice treated with mo, but no significant differences between mo subsets. Histological analyses 4 weeks after surgery showed an increased arteriole size in mice having received CD16+ mo, whereas the number of capillaries did not significantly differ between groups. CONCLUSIONS: Our findings suggest additive and differential effects of mo subsets during neovascularization processes, possibly due to an altered secretion of angiogenic factors and their paracrine capacity to stimulate new vessel formation. This article is protected by copyright. All rights reserved.