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

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.

Serum proteins and lipids in mild form of calf bronchopneumonia: candidates for reliable biomarkers

“…Thus, increased concentration and activity of gelatinases (MMP2 and MM9) were detected in lung lesion of calves with experimentally induced M. haemolytica pneumonia [4] and in tracheobronchial lavage fl uid of calves with concurrent infections of P. multocida and M. bovirhinis [49]. Hinds et al [30] using intravenous application of E. coli lipopolysaccharide as a model for acute phase protein responses showed that covalent MMP-9 haptoglobin complex (Hp-MMP-9) was detected in the serum before and declined more rapidly than other acute phase proteins, and assumed that Hp-MMP9 complex can be early and accurate markers of calf respiratory diseases. The serum level of Hp-MMP9 complex was confi rmed as a reliable biomarker of acute lung infl ammation in calves experimentally infected with M. haemolytica [46].…”

“…Back in 1982 Yates [29] pointed out that in different cases of calf bronchopneumonia the leukocyte counts could vary from leucocytosis to leukopenia. We believe that these variations are a result of 1) multifactorial aetiology of the disease, 2) potent immunomodulatory effects of microbiological causative agents [1] and 3) time-dependent fl uctuation in the number of leukocytes in peripheral blood after disease induction [30]. All of these factors must be taken into consideration before declaring increased peripheral blood leukocyte count as a suitable biomarker of calf bronchopneumonia.…”

“…Bovine IgG exist in several isotypic and allotypic variants [44] and can be differentially glycosylated [8] and more detailed analysis should be performed to precisely identify, which molecular variants of IgG are increased in bronchopneumonic calves. IgA in bovine serum exists exclusively in the dimeric form [45] and we think that the increase in the level of high molecular weight proteins in sera of bronchopneumonic calves might refl ect increased synthesis of IgA and IgM and/or some of high molecular weight acute phase proteins [30,46]. Precise identifi cation of constituents of the fraction of high molecular proteins requires further analysis.…”

Sequential changes in hepatic mRNA abundance and serum concentration of serum amyloid A in cattle with acute inflammation caused by endotoxin

“…In several studies aimed to evaluate time courses of SAA and other APPs, serum SAA increased in systemic inflammatory model cattle that endotoxin (ETX) challenged [ 4 , 12 , 28 ]. However, to the best of our knowledge, no studies have investigated sequential changes in mRNA expression of SAA isoform genes in ETX challenge model cattle.…”

Individual Reactivity of Granulocytic System of Newborn Calves and Its Role in Pathogenesis of Inflammatory Diseases of Respiratory and Gastrointestinal Tracts

“…SN activation is accompanied by the intensification of metabolic processes (respiratory explosion) and the secretion of large amount of antibacterial substances differing in chemical nature [15][16][17]. Such stereotyped reaction occurs to metabolites of microbial origin, for example, lipopolysaccharides (LPS's) of gram-negative bacteria [18], as well as to hormones, blood and tissue cell mediators, and various kinds of radiation [19][20][21][22].…”