Open AccessHMGB‐1 induces c‐kit + cell microvascular rolling and adhesion via both toll‐like receptor‐2 and toll‐like receptor‐4 of endothelial cells
Author(s) -
Furlani Dario,
Donndorf Peter,
Westien Ingeborg,
Ugurlucan Murat,
Pittermann Erik,
Wang Weiwei,
Li Wenzhong,
Vollmar Brigitte,
Steinhoff Gustav,
Kaminski Alexander,
Ma Nan
Publication year - 2012
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2011.01381.x
Subject(s) - toll like receptor , receptor , microbiology and biotechnology , tlr4 , cell adhesion molecule , chemistry , cell adhesion , biology , cell , immunology , innate immune system , biochemistry
High‐mobility group box 1 (HMGB‐1) is a strong chemo‐attractive signal for both inflammatory and stem cells. The aim of this study is to evaluate the mechanisms regulating HMGB‐1–mediated adhesion and rolling of c‐kit + cells and assess whether toll‐like receptor‐2 (TLR‐2) and toll‐like receptor‐4 (TLR‐4) of endothelial cells or c‐kit + cells are implicated in the activation of downstream migration signals to peripheral c‐kit + cells. Effects of HMGB‐1 on the c‐kit + cells/endothelial interaction were evaluated by a cremaster muscle model in wild‐type (WT), TLR‐2 (−/−) and Tlr4 (LPS‐del) mice. The mRNA and protein expression levels of endothelial nitric oxide synthase were determined by quantitative real‐time PCR and immunofluorescence staining. Induction of crucial adhesion molecules for rolling and adhesion of stem cells and leukocytes were monitored in vivo and in vitro . Following local HMGB‐1 administration, a significant increase in cell rolling was detected (32.4 ± 7.1% in ‘WT’ versus 9.9 ± 3.2% in ‘control’, P < 0.05). The number of firmly adherent c‐kit + cells was more than 13‐fold higher than that of the control group (14.6 ± 5.1 cells/mm 2 in ‘WT’ versus 1.1 ± 1.0 cells/mm 2 in ‘control’, P < 0.05). In knockout animals, the fraction of rolling cells did not differ significantly from control levels. Firm endothelial adhesion was significantly reduced in TLR‐2 (−/−) and Tlr4 (LPS‐del) mice compared to WT mice (1.5 ± 1.4 cells/mm 2 in ‘TLR‐2 (−/−)’ and 2.4 ± 1.4 cells/mm 2 in ‘Tlr4 (LPS‐del)’ versus 14.6 ± 5.1 cells/mm 2 in ‘WT’, P < 0.05). TLR‐2 (−/−) and Tlr4 (LPS‐del) stem cells in WT mice did not show significant reduction in rolling and adhesion compared to WT cells. HMGB‐1 mediates c‐kit + cell recruitment via endothelial TLR‐2 and TLR‐4.