Monocytes and Macrophages
Michael Fishbein. Role of macrophages in diagnostic
interpretation of endomyocardial biopsies.
Tim Johnson. Is transglutaminase the switch between
inflammation and scarring in chronic allogaft nephropathy.
David Kluth. Transfected macrophages in renal inflammation.
Alex Magil. Monocyte/macrophages in renal inflammation.
Jeremy Hughes. Resolution of injury, apoptosis and
macrophages.
Macrophage Localisation
From Gordon 2002
Differential Macrophage
Activation
IFN-
TNF
TGF
Histotoxic
NO generation
ADCC
etc
Reparative
IGF-1
Apoptotic cells
Inflammatory
Enzymes
Macrophages in Inflammation
Classical activation
Programmed
NO generation
Innate activation
Non-programmed
NO generation
How do macrophages integrate
conflicting signals ?
TNF
INF
IL-13
TGF
LPS
MCP-1
IL-10
IgG
IL-12
C3b
RANTES
Macrophage Programming
IFN
NO generation
CONTROL
30
TGF-BETA
IL-10
20
IL-6
10
IL-4
0
+4h
0h
-4h
TNF
60
Macrophages activated by certain
cytokines are refractory to other
activating cytokines
TNF
change %
40
20
TGF
0
-20
-40
-60
IFN
TNF
Monocytes and Macrophages
Michael Fishbein. Role of macrophages in diagnostic
interpretation of endomyocardial biopsies.
Alex Magil. Monocyte/macrophages in renal inflammation.
Jeremy Hughes. Resolution of injury, apoptosis and
macrophages.
David Kluth. Transfected macrophages in renal inflammation.
Tim Johnson. Is transglutaminase the switch between
inflammation and scarring in chronic allogaft nephropathy.
Michael Fishbein. Role of macrophages in diagnostic
interpretation of endomyocardial biopsies.
Distinguishing between acute rejection and Quilty lesions in
cardiac allograft biopsies.
• Quilty lesions contain B cells and T cells but very few
macrophages.
• Many macrophages in acute rejection.
Alex Magil. Monocyte/macrophages in renal inflammation.
Use of macrophage infiltration in diagnosis of humoral
rejection.
• Glomerular and tubulo-interstitial macrophages associated with
C4d deposition.
• Presence of macrophages associated with poor outcomes
Jeremy Hughes. Resolution of injury, apoptosis and
macrophages.
• Discussed the role of macrophages in disposal of dead
and dying cells.
• Macrophages the key cell in disposal of both necrotic and
apoptotic cells
• Described the multiple receptors responsible for uptake of
apoptotic cells, including the phosphydyl seriene receptor.
• Uptake of apoptotic cells induces an anti-inflammatory
phenotype in macrophages (and so does ligation of PSR)
• Overwhelming the normal mechanisms of disposal results
in inflammation.
David Kluth. Transfected macrophages in renal inflammation.
Discussed the various functional types of macrophages and showed
that anti-inflammatory macrophages can have profound effects in
vivo.
• Described the well recognised “phenotypes” - activated, innate activated,
alternatively activated, type 2 regulatory, and anti-inflammatory.
• Showed that thransfected macrophages expressing either IL-4 or IL-10 but
not TGF reduce acute experimental glomerular injury.
• These macrophages localise only to the kidney in which they are injected
but inflammation reduced in both kidneys.
• Introduction of macrophages with blocked NFB are also antiinflammatory, but only in the kidney into which the cells were injected
Localisation of cytokine
expressing macrophages
Recombinant Adenoviruses
Ad-IL-10
Ad-IL-4
Ad-TGF
1106 PKH26 labelled
transfected macrophages
injected into left renal
artery
David Kluth. Transfected macrophages in renal inflammation.
Discussed the various functional types of macrophages and showed
that anti-inflammatory macrophages can have profound effects in
vivo.
• Described the well recognised “phenotypes” - activated, innate activated,
alternatively activated, type 2 regulatory, and anti-inflammatory.
• Showed that thransfected macrophages expressing either IL-4 or IL-10 but
not TGF reduce acute experimental glomerular injury.
• These macrophages localise only to the kidney in which they are injected
but inflammation reduced in both kidneys.
• Introduction of macrophages with blocked NFB are also antiinflammatory, but only in the kidney into which the cells were injected
Tim Johnson. Is transglutaminase the switch between
inflammation and scarring in chronic allogaft nephropathy.
Discussed the role of tissue transglutaminases in cell death
and in matrix accumulation.
•Demonstrated all models of chronic renal scarring are associated
with increased expression of tissue transglutaminases.
•Expression associated with increased cross linking of collagen
and with increased TGF expression.
•Tubular cells were the source of tTGs in models of scarring in
native kidneys but interstitial (macrophages) in chronic scarring
in allografts.
Conclusions
Macrophages are numerous in all forms renal injury.
Macrophages have numerous different functions that may be
injurious or reparative.
Key issues for the future to devise a more complete
understanding of the range of macrophage activities, how to
identify macrophage “phenotypes” in vivo and how to
manipulate macrophage function as therapy.