Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

VI. Normal Plasma and Serum Proteins
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et al. , 2003 ; Heegaard et al. , 2000 ; Horadagoda et al. ,
1994 ). The mammary isoform of SAA (M-SAA3), which
is expressed and secreted in milk from mammary glands of
dairy cows with mastitis ( Eckersall et al. , 2001 ; Jacobsen
et al. , 2005b ; Nielsen et al. , 2004 ; Winter et al. , 2003 ), is
also found in milk from ewes with this condition ( Winter
et al. , 2003 ).
In the horse, SAA is a major APP with a large dynamic
range between the resting level in the healthy animal and
the concentrations obtained in serum from horses with
infection or inflammation ( Jacobsen and Andersen, 2007 ;
Pepys et al. , 1989 ; Stoneham et al. , 2001 ). Increased SAA
concentrations have been observed in horses following surgery,
with aseptic inflammation or arthritis, septicemia,
enteritis, pneumonia, and diarrhea ( Petersen et al. , 2004 ).
Measurement of the SAA concentration was found to be
of value in diagnosis of horses with colic, especially where
inflammation was the primary component of the pathogenesis
( Vandenplas et al. , 2005 ). Experimental infections
with equine herpesvirus and influenzavirus have also
resulted in an increase in the SAA concentration ( Hulten
et al. , 1999 ; Pepys et al. , 1989 ).
Determination of the SAA concentration may be similarly
useful in cats as it was shown to be the most rapidly
responding APP in a variety of inflammatory and
infectious conditions ( Kajikawa et al. , 1999 ), and the
cat is another species where CRP does not show a major
response. In the dog, the circulating concentration of SAA
does increase during an acute phase response and has
been observed in experimental parvovirus infection ( Yule
et al. , 1997 ) and in leishmaniasis ( Martinez-Subiela et al. ,
2002a ). However, with CRP becoming the primary canine
APP, it is likely that SAA will be used in a secondary role
in monitoring the acute phase response in this species. The
relationship of serum concentration of SAA with familial
amyloidosis as encountered in Siamese and Abyssinian
cats and Chinese shar-pei dogs remains to be fully elucidated
( Johnson et al. , 1995 ; Niewold et al. , 1999 ).
4 . α-1 Acid Glycoprotein
a . Biochemistry
Alpha-1 acid glycoprotein (AGP) is one of the most highly
glycosylated proteins in serum with a molecular mass of
around 43kD, of which approximately 45% is covalently
linked carbohydrate. These branched carbohydrate side
chains are composed of linked monosaccharides such as
mannose, galactose, and glucose with the final group in the
chain usually being sialic acid (N-acetyl-neuraminic acid).
Thus, negatively charged groups are located at the end
of each chain leading to the low pI of AGP of 2.8 to 3.8.
The sialic acid residues are also important for the structure
of the protein. Studies on feline AGP have revealed
that its branching degree was very low and that a decrease
in sialic acid expression occurred during infection with
feline infectious peritonitis virus ( Ceciliani et al. , 2004 ). In
feline leukemia virus infections, the degree of sialylation
was reduced in cats diagnosed with lymphoma ( Pocacqua
et al. , 2005 ). In contrast, feline AGP from cats with feline
immunodeficiency virus infection showed a wide range of
variation of the glycan chains .
b . Function and Pathophysiology
Though the precise role of AGP is not clear, it does bind
to a number of endogenous metabolites such as heparin,
histamine, serotonin, steroids, and catecholamines ( Israili
and Dayton, 2001 ). A related action of AGP is its ability to
bind to pharmacological compounds. This ability to bind
to drugs may have therapeutic implications as the amount
of drug bound can affect the free concentration of drug,
which is the metabolically active fraction. Increased AGP
because of an acute phase response may reduce the concentration
of free drug and could therefore affect pharmokinetics
( Ikenoue et al. , 2000 ). The ability of AGP to bind
low-molecular-weight ligands may also have a general
protective role as it binds to toxic lectins and endotoxins.
AGP also has several putative roles in the innate defense
against infection and modulating the immune reaction. It
can inhibit the attachment of Mycoplasma pneumoniae
to alveolar macrophages and can inhibit some strains of
influenza-virus. Furthermore, phagocytosis, neutrophil activation,
and platelet aggregation are inhibited by AGP, and it
may have a role in the maturation of T- and B-lymphocytes.
( Israili and Dayton, 2001 ). A biologically important alteration
of the glycosyl residue on AGP is the expression during
inflammatory disease of the sialyl Lewis-X antigen,
which is one of the major groups expressed on leukocytes
and is involved in leukocyte migration across the endothelium
( Degraaf et al. , 1993 ).
In most species, AGP is a moderate APP increasing
more slowly but also remaining elevated for longer than
the major APP such as canine CRP or bovine SAA and
Hp. However, this may be advantageous in diagnosis in
that inclusion of AGP in an acute phase profile would provide
information on conditions as they move from acute to
chronic. In a study of inflammatory disease in cattle, serum
from animals with chronic conditions had a higher proportion
of raised AGP than either SAA or Hp ( Horadagoda
et al. , 1999 ). Indeed the term “ acute phase protein ” is in
some ways a misnomer as it is not just acute conditions
that lead to the elevation of APP. Continued production of
at least some APP in chronic or subclinical disease may
be of equal importance to their appearance in acute conditions,
which can be more obvious to diagnose.
Feline AGP was found to be raised, though not as rapidly
as SAA, in a variety of inflammatory and infectious
diseases as well as postsurgery ( Kajikawa et al. , 1999 ). The
measurement of AGP in feline serum and peritoneal fluid
has become a recognized differential test for the identification
of feline infectious peritonitis ( Duthie et al., 1997 ;