Premium
The N‐terminal module of thrombospondin‐1 enhances superoxide generation from differentiated U937 human monocytic cells
Author(s) -
MartinManso Gema,
Mosher Deane F,
Roberts David D
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1146-b
Subject(s) - superoxide , innate immune system , thrombospondin 1 , u937 cell , nadph oxidase , microbiology and biotechnology , phagocyte , immune system , biology , monocyte , chemistry , reactive oxygen species , immunology , cancer research , biochemistry , phagocytosis , in vitro , enzyme , angiogenesis
Thrombospondin‐1 (TSP1) is a glycoprotein secreted by many cell types that modulates cell adhesion, growth, motility, differentiation, and survival. We investigated regulatory effects of TSP1 on phorbol ester (PMA)‐mediated superoxide generation from human U937 monocytic cells differentiated with recombinant human interferon‐gamma. Soluble TSP1 caused a significant increase in PMA‐mediated superoxide generation. Trimeric recombinant constructs containing the N‐modules, but not other recombinant regions of TSP1, replicated the activity of TSP1. A similar effect of TSP1 on superoxide generation has been described in human neutrophils. The superoxide‐generated via NADPH oxidase is an important component of the innate immune response. An important target of NADPH oxidase‐derived radicals is the ubiquitous transcription factor NF‐kappaB, which controls the expression of many genes involved in immune function and cell survival. Here we show that soluble TSP1 causes a significant increase in PMA‐mediated NF‐kappaB activation in human macrophages. Together, the present findings indicate that TSP1 enhances PMA‐mediated superoxide generation from human macrophages through its N‐terminal region, suggesting a physiological function of TSP1 in regulation of innate immune responses. This work was supported by Intramural Research Program, NCI, NIH, and by Instituto de Salud Carlos III.