Vitronectin is a critical protein adhesion substrate for IL‐4‐induced foreign body giant cell formation

Abstract

An in vitro system of interleukin (IL)-4-induced foreign body giant cell (FBGC) formation was utilized to define the adhesion protein substrate(s) that promotes this aspect of the foreign body reaction on biomedical polymers. Human monocytes were cultured on cell culture polystyrene surfaces that had been pre-adsorbed with a synthetic arginine-glycine-aspartate (RGD) peptide previously found to support optimal FBGC formation, or with various concentrations of potential physiological protein substrates, i.e. complement C3bi, collagen types I or IV, fibrinogen, plasma fibronectin, fibroblast fibronectin, laminin, thrombospondin, vitronectin, or von Willebrand factor. Cultures were evaluated on days 0 (1.5 hr), 3, and 7 by May-Grünwald/Giemsa staining. Initial monocyte adhesion occurred on all adsorbed proteins. However, by day 7 of culture, only vitronectin was striking in its ability to support significant macrophage adhesion, development, and fusion leading to FBGC formation. Vitronectin supported high degrees of FBGC formation at an absorption concentration between 5 and 25 μg per ml. These findings suggest that adsorbed vitronectin is critical in the collective events that support and promote FBGC formation on biomedical polymers, and that the propensity for vitronectin adsorption may underlie the material surface chemistry dependency of FBGC formation.

Adsorbed Fibrinogen Enhances Production of Bone- and Angiogenic-Related Factors by Monocytes/Macrophages

“…46 McNally et al observed lower monocyte/macrophage adhesion and no IL-4-induced FBGC formation on standard cell culture polystyrene preadsorbed with Fg when compared with RGD-coated substrates at all time points studied (0, 3 and 7 days). 37 On the other hand, others have found enhanced macrophage adhesion on different surfaces preadsorbed with Fg, relative to corresponding uncoated surfaces, 2 h and 1 day after cell seeding. 47 In addition, Yun et al showed that Fg preadsorbed onto poly(tetrafluoroethylene/ hexafluoropropylene) (FEP) copolymers induced higher monocyte adhesion on surfaces containing carboxyl groups compared with an FEP surface with only amine groups.…”

“…RGD was used as a positive control surface for macrophage development and adhesion and FBGC formation, as previously reported. [37][38][39] Adsorbed RGD is widely recognized for its adhesion-promoting capabilities in that it presents multiple copies of the RGD (arginine-glycine-aspartate) cell attachment sequence to integrin receptors, thus facilitating their engagement.…”

Гигантские Клетки Инородных Тел И Тканевые Реакции На Поверхности Имплантатов

“…Индуци-рованное IL-4 образование ГКИТ в условиях in vitro характеризуется экспрессией αM/β2, αX/β2, α5/β1, α2/β1 и α3/β1, что указывает на роль взаи-модействий фрагментов комплемента С3b, фиб-рина, фибриногена, фибронектина, фактора X и витронектина в местах имплантации биоматериа-лов. В процессе IL-4 зависимого формирования ГКИТ определена последовательность активности α-интегринов, которая, по данным Mc Nally et al, [42] следующая: αMβ2, αXβ2, α5β1> αVβ1> α3β1 и α2β1. В качестве лигандов ранней адгезии с β2 интегринами идентифицированы комплемент и фибриноген [42].…”

“…В процессе IL-4 зависимого формирования ГКИТ определена последовательность активности α-интегринов, которая, по данным Mc Nally et al, [42] следующая: αMβ2, αXβ2, α5β1> αVβ1> α3β1 и α2β1. В качестве лигандов ранней адгезии с β2 интегринами идентифицированы комплемент и фибриноген [42].…”

“…Одним из ключевых факторов поддержа-ния адгезии и слияния макрофагов на поверхно-сти биоматериалов является концентрация витро-нектина в составе их протеинового покрова. По-верхности, способствующие аккумуляции витро-нектина, способствуют и формированию ГКИТ [42]. Плазменный фибронектин также является модулирующим фактором образования ГКИТ.…”