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

VI. Normal Plasma and Serum Proteins
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represents the greatest proportion of plasma protein synthesized
during an acute phase response. Calculations have
been made in human medicine that during an acute phase
reaction approximately 12 g of muscle tissue has to be
degraded to provide the amino acids for 1 g of fibrinogen,
which, in common with most APP, has a higher proportion
of aromatic amino acids than muscle protein ( Preston
et al. , 1998 ). Assays for plasma fibrinogen have been
available for a long time. It is more consistently increased
during inflammation in horses and cattle than it is in dogs
and cats. The measurement of low plasma fibrinogen supports
a diagnosis of disseminated intravascular coagulation
( Mischke et al. , 1998 ), but it is not consistently decreased
in disseminated intravascular coagulation.
6 . Pig Major Acute Phase Protein (Inter-Alpha-Trypsin
Inhibitor Heavy Chain 4)
During the acute phase response in pigs, a major acute
phase protein (pig MAP) can be detected ( Lampreave et al. ,
1994 ) and has been identified as porcine inter-alpha-trypsin
inhibitor heavy chain 4 by comparison to the equivalent
human protein ( Gonzalez-Ramon et al. , 2000 ). This protein
of molecular mass 120 kDa is inducible by IL-6 in hepatocyte
culture. In serum during the acute phase response, its
concentration can increase by a factor of 30 compared to
healthy levels. Increases have been shown during infection
with A. pleuropneumonia (Heegaard et al. , 1998 ), in postweaning
multisystemic wasting disorder ( Segales et al. ,
2004 ), and following transport ( Saco et al. , 2003 ). A bovine
equivalent of this protein has been described that also displays
an acute phase response ( Pineiro et al. , 2004 ).
7 . Negative Acute Phase Proteins
Negative acute phase proteins are serum proteins that
decrease in concentration by greater than 25% during the
acute phase in response to infection, inflammation, and
trauma. The mechanism for the decrease in concentration
is not clear, but it can be rapid with significant reduction
found after 24 hours or it may be a more gradual decrease
over a period of days. Serum albumin is a negative acute
phase protein, and the concentration of this protein falls
gradually with the reduction in concentration being more
noticeable in chronic inflammatory disease. Transferrin,
the iron transport protein of serum ( Gomme and Mccann,
2005 ), has also been described as a negative APP, but
the major diagnostic application of measuring its serum
concentration is in relation to its role in diseases of iron
metabolism (Chapter 9) . Its analogue in chickens, ovatransferrin,
is a positive APP ( Tohjo et al. , 1995 ; Xie et al. ,
2002a, 2002b ).
More rapidly reacting negative APP have been identified.
Porcine apolipoprotein A-1 ( Navarro et al. , 2004 )
decreased in concentration by 50% to 80% within 2 to 5
days of experimental infection with Streptococcus suis or A.
pleuropneumoniae (Carpintero et al. , 2005 ). As this apolipoprotein
is associated with HDL, it appears to have a reverse
relation with SAA (which also binds to this lipoprotein).
Transthyretin (TTR) and retinal binding protein (RBP) are
related transport proteins, which in rats show a decrease during
the acute phase reaction ( Rosales et al. , 1996 ), but their
pathophysiology has not been fully elucidated in domestic
animals. In addition, the interpretation of a fall in serum
concentration of these proteins is complicated because they
are also affected by nutritional status. TTR is a thyroxine
binding protein, which in human serum has a higher electrophoretic
mobility than albumin and was therefore originally
known as prealbumin. However, in most domestic
species, TTR has a lower mobility and no prealbumin is
observed (see Fig. 5-2 ). In the circulation it forms a complex
with RBP, which in turn binds to retinol (vitamin A).
Infection of pigs with S. suis caused a significant reduction
of the TTR concentration in serum, showing that it was a
negative APP in this species ( Campbell et al. , 2005 ).
C . Complement Proteins
Complement is a group of interacting serum proteins that
participate in a cascade of reactions, resulting in opsonization
of foreign cells and particles ( Gorman and Halliwell,
1989a ). Complement is activated by the “ classical ” or
“ alternative ” pathways, terminology based on the time
frame of discovery rather than on the relative importance
of the pathway concerned. The complement proteins
are a series of zymogens, which on activation are able
to specifically activate another member of the cascade
by proteolytic cleavage. Activation of the classical pathway
occurs by binding of complement C1q to initiating factors
such as antigen-antibody complexes or C-reactive protein
bound to bacterial pathogen. The alternative pathway does
not need antibody for activation but can be stimulated by
mediators such as parasites, viruses, bacteria, and tumor
cells. Both pathways lead to the formation of a membrane
attack complex composed of components C5, C6, C7, C8,
and C9, which cause lysis of cell membranes. More than a
dozen complement proteins have been identified, but apart
from a minor positive acute phase response that has been
observed for component C3, the most use in diagnosis of
disease is in assessment of complement deficiency in relation
to immune function. These are covered in Chapter 6 as
part of the discussion on clinical immunology.
D . Immunoglobulins
On SPE, most immunoglobulins are found in the γ -globulin
fraction, which can be differentiated into γ 1 and γ 2 . Of