Biochemical and enzymatic characterization of purified covalent complexes of matrix metalloproteinase-9 and haptoglobin released by bovine granulocytes in vitro

Bannikov, G. A.; Mattoon, John S.; Abrahamsen, Eric J; Premanandan, Christopher; Green‐Church, Kari B.; Marsh, Antoinette E.; Lakritz, Jeffrey

doi:10.2460/ajvr.68.9.995

Cited by 16 publications

(23 citation statements)

References 48 publications

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“…Bannikov et al (2007) reported that neutrophil MMP-9 is covalently complexed with neutrophil synthesized Hp suggesting that this is a potentially useful biomarker indicating activation and degranulation of neutrophils (Theurer et al, 2013). Increases in plasma Hp-MMP-9 concentration over time are consistent with other studies reporting significantly elevated plasma Hp-MMP-9 concentrations in cattle with acute inflammation (Bannikov et al, 2011).…”

Section: Haptoglobin-matrix Metalloproteinase-9 Complexessupporting

confidence: 81%

Impact of oral meloxicam on circulating physiological biomarkers of stress and inflammation in beef steers after long-distance transportation1

Engen

Stock

Engelken

et al. 2014

Journal of Animal Science

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Transportation stress can result in significant economic losses to producers due to decreased animal productivity and increased medication costs associated with sickness such as bovine respiratory disease (BRD). Meloxicam (MEL) provides pain relief and anti-inflammatory effects in cattle for several days after a single oral treatment. Our hypothesis was that MEL administration before shipping would reduce the impact of long-distance transportation on circulating physiological biomarkers of stress and inflammation in beef steers. Ninety-seven beef steers were blood sampled for baseline biomarker determination and then randomly assigned to receive either 1 mg/kg MEL (n = 49) or a placebo (CONT; n = 48) per os before a 1,316-km transportation event lasting approximately 16 h. Calves were then blood sampled on arrival and 5 d later. Changes in the hemogram, circulating plasma proteins, total carbon dioxide (TCO 2 ), fibrinogen, substance P (SP), cortisol, haptoglobin (Hp)-matrix metalloproteinase-9 (MMP-9) complexes, and tumor necrosis factor α (TNFα) between treatments over time were compared using a mixed effects model with statistical significance designated as P < 0.05. Analysis of covariance was conducted to assess the relationship between circulating MEL concentrations and biomarker changes over time. An increase in neutrophil, platelet, monocyte, white blood cell, and red blood cell counts occurred after transportation (P < 0.0001) and a decrease in lymphocyte count were observed (P < 0.0001). Meloxicam treatment reduced the stress-induced neutrophilia (P = 0.0072) and circulating monocyte count (P = 0.013) on arrival. Mean corpuscle hemoglobin (P = 0.05), mean corpuscle volume (P = 0.05), and lymphocyte count (P = 0.05) were also greater in the CONT calves compared with MEL calves after transportation. Furthermore, Hp-MMP-9 complexes, TCO 2 , TNFα, plasma proteins, and SP increased and cortisol decreased after shipping (P < 0.01). Meloxicam treatment tended to reduce serum cortisol concentrations (P = 0.08) and there was evidence of a time × treatment interaction (P = 0.04). An inverse relationship between plasma MEL concentrations and circulation cortisol concentrations (P = 0.002) and neutrophil (P = 0.04) and basophil counts (P = 0.03) was also observed. The results suggest that MEL administration may reduce the impact of long-distance transportation on circulating physiological biomarkers of stress and inflammation in beef calves. ABSTRACT: Transportation stress can result in significant economic losses to producers due to decreased animal productivity and increased medication costs associated with sickness such as bovine respiratory disease (BRD). Meloxicam (MEL) provides pain relief and anti-inflammatory effects in cattle for several days after a single oral treatment. Our hypothesis was that MEL administration before shipping would reduce the impact of long-distance transportation on circulating physiological biomarkers of stress and inflammation in beef steers. Ninety-seven beef steers were b...

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Section: Haptoglobin-matrix Metalloproteinase-9 Complexessupporting

confidence: 81%

Impact of oral meloxicam on circulating physiological biomarkers of stress and inflammation in beef steers after long-distance transportation1

Engen

Stock

Engelken

et al. 2014

Journal of Animal Science

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“…34 Complexes of MMP-9 and Hp have been detected in sera of cows with acute inflammation, but not in clinically normal cows or cows with chronic disease. 35 The interaction between Hp and MMP in aneurysm development has not been fully investigated. A functional study performed by de Kleijn et al revealed that Hp inhibits the activity of MMP-2 by 50% and MMP-9 by 30% in cultured arterial smooth muscle culture cells, but increases the production of gelatin in arterial smooth muscle cells in Hp knockout mice.…”

Section: Discussionmentioning

confidence: 99%

Haptoglobin phenotypes and plasma haptoglobin levels in patients with abdominal aortic aneurysm

Pan

Cheng

Shih

et al. 2011

Journal of Vascular Surgery

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“…In the previous work, we demonstrated that phorbol ester stimulation of isolated peripheral blood neutrophils are is associated with appearance of Hp-MMP 9 complexes in culture medium within 30 minutes [22]. We also identified covalent, heteromeric complexes of Hp in complex with matrix metalloproteinase 9 (Hp-MMP 9), within the serum of cattle with clinically apparent acute onset of septic inflammation of the abdomen or thorax [23].…”

Section: Introductionmentioning

confidence: 99%

“…In contrast to free serum Hp, whose main source is the liver during inflammation, serum Hp-MMP 9 complexes are only produced by neutrophils. As such, Hp-MMP 9 complexes, in serum, represent neutrophil degranulation [22]. …”

Section: Introductionmentioning

confidence: 99%

“…The kinetics of most APP involves recognition of pathogens/pathogen products, mediator production and release, gene expression and protein synthesis and release of protein into the circulation [28–32]. Release of neutrophil granule proteins is rapid after in vitro stimulation, occurring within 30 minutes of phorbol ester treatment [22]. The objective of the present study was to characterize the time course of serum Hp-MMP 9 complex appearance in relation to changes in the hemogram, serum C concentrations and by comparing with other acute phase proteins in calves (Hp, SAA, AGP).…”

Section: Introductionmentioning

confidence: 99%

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Characterization of the contributions of Hp-MMP 9 to the serum acute phase protein response of lipopolysaccharide challenged calves

et al. 2014

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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.

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Biochemical and enzymatic characterization of purified covalent complexes of matrix metalloproteinase-9 and haptoglobin released by bovine granulocytes in vitro

Abstract: A fraction of neutrophil MMP-9 is released in complex with haptoglobin. The complex is present in granules and retains biological activity of its components. Detection of the complex in serum may provide an indicator of acute inflammation.

Cited by 16 publications

References 48 publications

Impact of oral meloxicam on circulating physiological biomarkers of stress and inflammation in beef steers after long-distance transportation1

Impact of oral meloxicam on circulating physiological biomarkers of stress and inflammation in beef steers after long-distance transportation1

Haptoglobin phenotypes and plasma haptoglobin levels in patients with abdominal aortic aneurysm

Characterization of the contributions of Hp-MMP 9 to the serum acute phase protein response of lipopolysaccharide challenged calves

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