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From: TSS ()
Subject: Re: Amyloidogenic potential of foie gras
Date: June 22, 2007 at 2:26 pm PST
In Reply to: Amyloidogenic potential of foie gras posted by TSS on June 22, 2007 at 2:23 pm:
Vet Pathol 40:7180 (2003)
Pathology of AA Amyloidosis in Domestic Sheep and Goats
C. MEŽ NSUA, L. CARRASCO, M. J. BAUTISTA, E. BIESCAS, A. FERNAŽ NDEZ, C. L.
MURPHY, D. T. WEISS,
A. SOLOMON, AND L. LUJAŽ N
Department of Animal Pathology, University of Zaragoza, Veterinary Faculty,
Zaragoza, Spain (CM, EB, AF, LL);
Department of Anatomy and Comparative Pathology, University of CoŽrdoba,
Veterinary Faculty, Campus de Rabanales,
CoŽrdoba, Spain (LC, MJB); and Human Immunology and Cancer Program,
University of Tennessee Graduate School of
Medicine, Knoxville, TN (CLM, DTW, AS)
Abstract. We describe the main pathologic changes in small ruminants
affected by AA amyloidosis, together
with the partial sequence of the protein involved. Twenty-one sheep and one
goat were selected for
presenting macroscopic kidney lesions compatible with systemic amyloidosis.
Available tissue samples were
studied by histologic, immunopathologic, and ultrastructural means. Renal
lesions were characterized grossly
by pale cortical surfaces with scattered, miliary, whitish-yellow foci and
on cut cortical surfaces by straight,
whitish-yellow striations. Gangrenous pneumonia was observed in 16 out of 21
affected sheep (76.2%), although
other chronic inflammations were also observed. Amyloid was detected in all
grossly affected kidneys using
Congo red staining, lesions being most remarkable in glomeruli, affecting
95.5% of animals studied. Congophilic
deposits were also observed in intertubular interstitium (68.2%) and medulla
(57.1%). All amyloid-affected
animals presented proximal convoluted tubule lesions, mostly characterized
by an increase in diameter and by
hyaline granular degeneration that were responsible for the macroscopic
appearance of the kidney. Histologically,
amyloid was also seen in blood vessels, spleen, liver, lymph nodes,
gastrointestinal tract, and adrenal
glands. All amyloid deposits demonstrated greenish-yellow birefringence with
polarized light, and the antisera
prepared against goat amyloid extracts specifically reacted with
birefringent congophilic deposits of both sheep
and goats. Ultrastructurally, these deposits were formed by masses of
straight, nonbranching fibrils located
predominantly in the basement membranes of glomerular capillaries and in the
mesangium. Partial sequence of
the protein in sheep and goats indicated a high degree of homology with the
previously reported sequence of
sheep Serum Amyloid A.
Key words: AA amyloidosis, amyloid, goats, kidney, sheep, small ruminants.
snip...
To the best of our knowledge this is the first comprehensive
pathologic study on AA amyloidosis in domestic
small ruminants. AA amyloidosis has been previously
reported incidentally in domestic sheep and
goats.33,39 Amyloidosis was also seen in a goat infected
by caprine arthritis encephalitis virus, although no detailed
description was provided.6 Some sheep that were
experimentally inoculated to obtain hyperimmune sera
and a goat that suffered numerous protein inoculations
also developed amyloidosis.9,13 Remarkably, the only
detailed study on reactive amyloidosis in small rumi78
Vet Pathol 40:1, 2003 MeŽnsua, Carrasco, Bautista, Biescas, FernaŽndez,
Murphy, Weiss, Solomon, and LujaŽn
nants was done in wild bighorn sheep and in captive
Dall sheep, where a pathologic condition similar to the
one described in this study was presented.11,18,45
We found in our sheep and goat that, as previously
observed in these species as well as in cows,16,18,26,33,39
bighorn sheep,11 and Dorcas gazelles,32 the organ most
involved was the kidney. The kidney was the only organ
harboring macroscopic lesions that consisted of
miliary foci on the cortical surface of the kidney and,
on cut surfaces, radial striations located only in the
renal cortex. We attribute these features to a resorptive,
proteinaceous tubulonephrosis that affected the convoluted
proximal tubules and occurred as a consequence
of protein loss through impaired glomeruli by
the deposition of amyloid. Therefore, the macroscopic
picture did not directly reflect the amount of renal amyloid
but merely represented the degree of proximal
convoluted tubulonephrosis (notably, the tubular epithelial
cells were not congophilic). A similar conclusion
had been made in the case of bovine renal AA
amyloidosis.10,26
Remarkably, our animals exhibited no gross amyloid-
related abnormalities in organs besides the kidney.
This finding is in contrast to the pattern of AA deposition
in other species of small ruminants, as well as
horses and experimental rodents, where amyloid was
found to be most pronounced in spleen, liver, adrenal
glands, and gastrointestinal tract.9,11,22,40,45,47 This difference
in tissue distribution of AA amyloid among
animal species suggests that particular host factors,
e.g., accessory molecules such as proteoglycans that
codeposit with the amyloidogenic protein,37 may be
involved in this phenomenon. Alternatively, the presence
of multiple, SAA isoforms in sheep and goats,
such as found in mice, cows, and humans, may account
for organ selectivity.1,43
Microscopically, we found that the amyloid deposits
in sheep and goat were predominantly located within
the glomeruli and, to a lesser degree, the medulla, as
found in dogs and occasionally in cattle.7,16,26 However,
AA amyloid deposits were observed almost exclusively
in the medulla of Dorcas gazelles,32 and others authors
have found it most frequently in the renal medulla
of cows.10 Initially, the amyloid in our animals
was localized to the glomerular capillary subendothelium,
as also seen in the cow,28 but as the disease
progressed, involved additional areas of the kidney.
Ultrastructurally, the lesions were similar to those described
in other species and included thickening of the
basement membrane and fusion of podocyte foot processes.
23,32 Only in the most advanced cases, with the
glomerulus being in a terminal stage, was a mononuclear
cell interstitial infiltrate noted.
AA amyloidosis characteristically develops in humans
and animals as a consequence of a long-standing,
chronic infectious or inflammatory process. Most of
our affected sheep had gangrenous pneumonia, an
acute process that normally became chronic in sheep
(L. LujaŽn, personal observation). However, other animals
in the study were free of this type of pneumonia
and were affected by other primary inflammatory foci
such as pseudotuberculosis or abscesses. These results
are concordant with causes previously studied for domestic
and wild small ruminants, where chronic suppurative
pneumonias, Corynebacterium pseudotuberculosis,
and Actinomyces pyogenes, were the primary
inflammatory diseases.11,18,32,39,45 Gangrenous pneumonia
typically develops when contaminated foreign bodies
are introduced into the airways,17 but we were unable
to find any recognizable foreign material within
the lesions. However, over the years, we have found
several cases with vegetal fragments in the bronchi
causing pulmonary gangrene and amyloidosis. This
process seems to be relatively high in adult sheep of
our geographic area. In countries where such pneumonias
are not important, the appearance of AA amyloidosis
is likely to be minimal.
Another amyloid form described in ruminants is
APrPsc, the amyloid detected in animals suffering from
transmissible spongiform encephalopathies. This form
of amyloidosis is observed in scrapie of sheep and
goats and also in a few cases of bovine spongiform
encephalopathy.3,42,44 In our study, no CR-positive areas
were seen in the nervous system parenchyma thus
indicating that these two amyloid forms seem to be
unrelated.
Further investigations into the different SAA isoforms,
their involvement in amyloidogenesis, and the
experimental reproduction of the gangrenous pneumonia
and systemic AA amyloidosis in sheep are currently
being performed. ........
TSS
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