ORGAN SPECIFIC ACUTE PHASE PROTEINS IN ANIMALS
Niewold Theo1, Meinen Margrit2
1
Animal Sciences Group of Wageningen UR, Research Cluster: Animal Physiology and
Health, P.O. Box 65, 8200 AB Lelystad, the Netherlands
E-mail: theo.niewold@wur.nl
2
University of Utrecht, Faculty of Veterinary Medicine, Department of Farm Animal Health,
Utrecht, The Netherlands
The acute phase reaction (APR) is a physiological systemic reaction to local or
systemic disturbances such as infection, tissue injury, trauma or surgery, neoplastic or
immunological disorders. The APR occurs early and independent of the origin of the
inflammation. During the APR, pro-inflammatory cytokines are released into the circulation.
Within hours hepatic protein synthesis is altered, resulting in a decrease or increase in liverderived serum proteins, the acute phase proteins (APP). APP were first used in human clinical
medicine to monitor the progression of (inflammatory) disease. Subsequently, APP have
found similar application in the veterinary field, in laboratory rodents, and later in husbandry
animals. APP are promising indicators of disease and welfare in animals (Eckersall, 2000).
One of the great advantages of the classic APP is that they are a systemic and non-specific
response to a host of pathological processes. This gives it great potential for high-throughput
testing such as is required for application in the slaughterhouse, and for the monitoring of
general health and welfare. However, the same property makes it less suited for the diagnosis
of diseases of specific organ systems. So called local or tissue-specific isoforms of the acute
phase protein serum amyloid A (SAA) have been found in the circulation. However, these
isoforms are not likely to be really tissue-specific in the sense that elevated levels can be
related to one specific organ. Of the local SAA proteins, only SAA3 found in milk is specific
for udder injury (Gronlund et al, 2003).
In the clinic, there is a definite need for new biochemical markers for tissue-specific
injury.
Similar to what happened with APP, now in human medicine the development of
organ specific indicators proceeds veterinary use. Examples of these markers are the fatty acid
binding proteins (FABP), and pancreatitis associated protein (PAP). FABP is a family of
intracellular, constitutive proteins, which are released into the blood after organ injury. FABP
are not APP sensu strictu since they are not induced by inflammatory mediators, and synthesis
is not upregulated after injury. Plasma levels are proportional to the amount of damage, and
reflect the amount of cells affected. There are at least nine different cytoplasmatic FABPs, all
with a characteristic tissue distribution (Glatz and van der Vusse, 1996). Not all are restricted
to one organ system, but intestinal FABP (I-FABP) is. In humans, determination of plasma
levels of I-FABP has found use in the early detection of intestinal injury due to various
conditions, and in the monitoring of (post-operative) healing (Pelsers et al, 2003). Also in
humans, heart-FABP (H-FABP) despite being not restricted to the heart, has been proven to
be a very useful serum marker for measurement of myocardial infarct size (de Groot et al,
1999). Apart from laboratory animals, data on the use of FABP as markers in domestic
animals is just emerging. Recently, the use of I-FABP as a marker for ischemic intestinal
damage in pigs has been described (Niewold et al, 2004). Furthermore, preliminary data show
that I-FABP levels are indicators of rotaviral infection in pigs, and of bovine virus diarrhea
virus (BVDV) infection in calves. An additional advantage of FABPs is that since they are
small proteins (14-15 kDa), detection in urine is also possible.
Another example of a tissue-specific marker is PAP. PAP is a C-type lectin, with antiinflammatory properties. PAP was originally described as a marker for pancreatitis (Nordback
et al., 1995). In recent years, it became clear that PAP is also produced in the intestine, most
likely in Paneth cells. In laboratory rodents, and in humans it was demonstrated that the serum
levels of PAP is a good indicator of intestinal inflammatory conditions (Desjeux et al., 2002).
There are as yet no data on PAP in domestic animals, but our own preliminary data show PAP
to be present in pig small intestine, and that its synthesis is upregulated after infection.
In this presentation, we review the clinical use of circulating proteins which are
associated with specific organ damage. It is argued that proteins like FABPs and PAP which
are already widely used in human medicine should be used similarly in veterinary medicine.
Assays for organ and tissue specific damage will find broad application in animal husbandry
and for pets. First, it can function as an objective test for the assessment of intestinal health of
production animals in different environments and management systems. This could include
intensive versus more extensive farming, different feeding regimens etcetera. It will also
contribute to health monitoring of farms, and will be used diagnostically by veterinarians.
We conclude that organ specific acute phase proteins will be a valuable addition to the
classic APP.
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