Activated renal macrophages are markers of disease onset and disease remission
in lupus nephritis.
Authors Schiffer L, Bethunaickan R, Ramanujam M, Huang W, Schiffer M, Tao H, Madaio MP,
Bottinger EP, Davidson A
Submitted By Submitted Externally on 9/2/2015
Status Published
Journal Journal of immunology (Baltimore, Md. : 1950)
Year 2008
Date Published 2/1/2008
Volume : Pages 180 : 1938 - 1947
PubMed Reference 18209092
Abstract Costimulatory blockade with CTLA4Ig and anti-CD40L along with a single dose of
cyclophosphamide induces remission of systemic lupus erythematosus nephritis in
NZB/W F(1) mice. To understand the mechanisms for remission and for impending
relapse, we examined the expression profiles of 61 inflammatory molecules in the
perfused kidneys of treated mice and untreated mice at different stages of
disease. Further studies using flow cytometry and immunohistochemistry allowed
us to determine the cellular origins of several key markers. We show that only a
limited set of inflammatory mediators is expressed in the kidney following
glomerular immune complex deposition but before the onset of proteinuria.
Formation of a lymphoid aggregate in the renal pelvis precedes the invasion of
the kidney by inflammatory cells. Regulatory molecules are expressed early in
the disease process and during remission but do not prevent the inevitable
progression of active inflammation. Onset of proliferative glomerulonephritis
and proteinuria is associated with activation of the renal endothelium,
expression of chemokines that mediate glomerular cell infiltration, and
infiltration by activated dendritic cells and macrophages that migrate to
different topographical areas of the kidney but express a similar profile of
inflammatory cytokines. Increasing interstitial infiltration by macrophages and
progressive tubular damage, manifested by production of lipocalin-2, occur later
in the disease process. Studies of treated mice identify a type II
(M2b)-activated macrophage as a marker of remission induction and impending
relapse and suggest that therapy for systemic lupus erythematosus nephritis
should include strategies that prevent both activation of monocytes and their
migration to the kidney.


Investigators with authorship
NameInstitution
Erwin BottingerMount Sinai School of Medicine

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