Abstract

BackgroundBovine respiratory disease (BRD) is a costly feature of modern cattle production. Early and accurate detection of BRD may prove useful in the successful management of this disease. The primary objective of the study was to define the time course of covalent complexes of neutrophil, haptoglobin (Hp) and matrix metalloproteinase 9 (Hp-MMP 9) in serum after intravenous lipopolysaccharide (LPS) in comparison to traditional markers. Our hypothesis was that serum concentrations of neutrophil Hp-MMP 9 provides information distinct from traditional acute phase protein markers. To characterize the neutrophil responses to lipopolysaccharide (E. coli; O111:B4; 2.5 μg/kg body weight), nine healthy, Jersey calves (65-82 days of age; 74.5 ± 13.1 kg) were challenged and physiologic parameters, peripheral blood cell counts and serum cortisol (C), Hp-MMP 9, Hp, alpha1-acid glycoprotein (AGP), serum amyloid A (SAA) were obtained starting 24 hours before to 96 hours post-LPS challenge.ResultsPhysiologic parameters (temperature, pulse, respiratory rate) and attitude assessed at each time point indicated that LPS challenge resulted in rapid onset of depression, tachypnea, leukopenia, neutropenia and lymphopenia within 1 hour. Serum C concentrations were significantly increased by 1 hour post-LPS. Serum Hp-MMP 9 complexes were detectable in serum by 0.5 hours and peaked at 16 h, serum total Hp remained <10 μg/mL until 8 hours post LPS infusion and were significantly greater than baseline by 12 hours post-LPS infusion. Serum amyloid A concentrations increased significantly by 8 hours post LPS. Serum concentrations of AGP increased significantly by 16 hours post LPS. Serum concentrations of Hp, SAA and AGP remained significantly greater than baseline out to 96 hours post-LPS. The total systemic exposure to traditional makers is significantly greater than from Hp-MMP 9ConclusionUsing a well described model for acute phase protein responses, the data demonstrate that serum neutrophil Hp-MMP 9 complexes appear sooner and decline more rapidly than other acute phase proteins (APP). Since Hp-MMP9 is stored pre-formed, it provides information specifically addressing the LPS-induced activation of bovine neutrophils. Contributions of Hp-MMP 9 to the serum acute phase protein response may provide useful information, independent of hepatic responses, in diagnosis of acute inflammation.

Highlights

  • Bovine respiratory disease (BRD) is a costly feature of modern cattle production

  • When serum Hp, serum amyloid A (SAA) and acid glycoprotein (AGP) were evaluated under field conditions, serum concentrations of Hp were more useful in predicting the presence of respiratory disease and response to therapy, whereas SAA and AGP did not discriminate between animals which became sick and those that did not [21]

  • We propose that Hp-MMP 9 complexes, observed after phorbol ester stimulation of isolated peripheral blood neutrophils in vitro and found in acute phase sera, have specific functional significance differing from un-complexed forms of Hp or MMP 9 alone and as a consequence, serum concentrations of Hp-MMP 9 may serve as an independent indicator of clinically important events occurring during acute inflammation

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Summary

Introduction

Bovine respiratory disease (BRD) is a costly feature of modern cattle production. Early and accurate detection of BRD may prove useful in the successful management of this disease. Other acute phase proteins, such as serum amyloid A (SAA) and alpha 1 acid glycoprotein (AGP) have been studied in cattle undergoing LPS-challenge and experimental or naturally occurring disease [1,14,19,20]. Several studies indicate that LPS- challenge or experimental bacterial infection elicited earlier increases in serum SAA concentrations, suggesting SAA is more sensitive than Hp due to more rapid production and release [1,14,19,20]. When serum Hp, SAA and AGP were evaluated under field conditions, serum concentrations of Hp were more useful in predicting the presence of respiratory disease and response to therapy, whereas SAA and AGP did not discriminate between animals which became sick and those that did not [21]

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