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Adoptive transfer of nuclear factor-kappaB-inactive macrophages to the glomerulus.

Abstract：

BACKGROUND:Macrophages have been regarded as "blackguards" in the generation of glomerular injury. However, it is still unclear what kind of cellular machinery is responsible for their pathogenic actions. To explore this issue, this investigation aims at developing a novel strategy using adoptive transfer of "loss-of-function" macrophages to the glomerulus. As a prototypal investigation, this study examines a role for nuclear factor-kappaB (NF-kappaB) in effector actions of macrophages within the glomerular microenvironment. METHODS:NF-kappaB-inactive macrophages, NIKMACNR, were created by transduction of NR8383 rat macrophages with retrovirus encoding a super-repressor mutant of IkappaBalpha, IkappaBalphaM. The effector functions of NIKMACNR cells on resident cells were evaluated by coculture, cross-feeding, and in vivo macrophage transfer. RESULTS:Rat mesangial cells cocultured with control macrophages showed abundant expression of activation markers, including monocyte chemoattractant protein-1, stromelysin, and gelatinase B. In contrast, coculture with NIKMACNR macrophages induced only modest gene expression. Similarly, culture medium conditioned by activated, control macrophages triggered mesangial cells and isolated glomeruli to express the activation markers, whereas the stimulatory effect was not observed in medium conditioned by NIKMACNR macrophages. To evaluate effector actions of NIKMACNR macrophages in the glomerulus, control macrophages and NIKMACNR cells were transferred into normal rat glomeruli via renal artery injection. After the transfer of control macrophages, substantial induction of the activation marker stromelysin was observed in resident glomerular cells. This induction was dramatically diminished in the glomeruli transferred with NIKMACNR macrophages. CONCLUSIONS:Inactivation of NF-kappaB in macrophages effectively disrupted paracrine, stimulatory loops from macrophages to resident glomerular cells. A combination of "loss-of-function" strategies with the technique for adoptive cell transfer is thus useful to explore pathophysiologic roles for certain machinery of macrophages within the glomerulus.

journal_name

Kidney Int

journal_title

Kidney international

authors

Kitamura M

doi

10.1046/j.1523-1755.2000.00893.x

subject

Has Abstract

pub_date

2000-02-01 00:00:00

pages

709-16

issue

eissn

0085-2538

issn

1523-1755

pii

S0085-2538(15)46789-4

journal_volume

pub_type

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Adoptive transfer of nuclear factor-kappaB-inactive macrophages to the glomerulus.