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Infection and Immunity, July 2004, p. 3777-3782, Vol. 72, No. 7
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.7.3777-3782.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

ITIH4 (Inter-Alpha-Trypsin Inhibitor Heavy Chain 4) Is a New Acute-Phase Protein Isolated from Cattle during Experimental Infection

Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, 50009 Zaragoza, Spain,¹ Department of Clinical Veterinary Sciences, Faculty of Veterinary Medicine, University of Helsinki, Saari Unit, FIN-04920 Saarentaus, Finland,² Department of Immunology and Biochemistry, Danish Veterinary Institute, DK-1790 Copenhagen V,³ Department of Virology, Danish Veterinary Institute, Lindholm, DK-4771 Kalvehave, Denmark⁴

Received 1 December 2003/ Accepted 17 March 2004

We have isolated from calf serum a protein with an apparent M_r of 120,000. The protein was detected by using antibodies against major acute-phase protein in pigs with acute inflammation. The amino acid sequence of an internal fragment revealed that this protein is the bovine counterpart of ITIH4, the heavy chain 4 of the inter-alpha-trypsin inhibitor family. The response of this protein in the sera was determined for animals during experimental bacterial and viral infections. In the bacterial model, animals were inoculated with a mixture of Actinomyces pyogenes, Fusobacterium necrophorum, and Peptostreptococcus indolicus to induce an acute-phase reaction. All animals developed moderate to severe clinical mastitis and exhibited remarkable increases in ITIH4 concentration in serum (from 3 to 12 times the initial values, peaking at 48 to 72 h after infection) that correlated with the severity of the disease. Animals with experimental infections with bovine respiratory syncytial virus (BRSV) also showed increases in ITIH4 concentration (from two- to fivefold), which peaked at around 7 to 8 days after inoculation. Generally, no response was seen after a second infection of the same animals with the virus. Because of the significant induction of the protein in the animals in the mastitis and BRSV infection models, we can conclude that ITIH4 is a new positive acute-phase protein in cattle.

Editor: S. H. E. Kaufmann

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