Negative acute phase proteins

These are proteins whose plasma concentrations increase (positive acute-phase proteins) or decrease (negative acute-phase proteins) in response to inflammation. This response is called the... 

Acute-phase proteins are a class of proteins whose plasma concentrations increase (positive acute-phase proteins) or decrease (negative acute-phase proteins) in response to inflammation. This response is called the acute-phase reaction (or acute-phase response). In response to injury, local inflammatory cells secrete a number of cytokines into the bloodstream, the most notable of which are the interleukins (IL-1, IL-6, IL-8) and TNF-a. The liver responds by producing a large number of acute-phase reactants or reducing the production of others. 

Interpretation of plasma concentrations of retinol is confounded by the fact that both RBP and transthyretin are negative acute phase proteins, and their synthesis falls, and hence the plasma concentration of retinol fall, in response to infection. Similarly, both protein-energy malnutrition and zinc deficiency result in a low plasma concentration, despite possibly adequate liver reserves as a result of impaired synthesis of RBP. 

The alterations in serum proteins (acute phase response) that occur within a few hours to a few days after tissue injury due to infection, trauma, bums, surgery, or infarction and inflammatory condition are divided into two categories. The first category includes those proteins that are increased by at least 25% (positive acute phase proteins), and the second category includes proteins that are decreased by at least 25% (negative acute phase proteins). 

Examples of positive and negative acute phase proteins are given in Table VI-1. C-reactive protein and serum amyloid A are elevated in serum by as much as 1000-fold from their basal values. Serum amyloid A is an apolipoprotein it is synthesized in hepatocytes in response to inflammatory stimuli and associated with HDL. The function of serum amyloid A is not clear and it is not commonly measured as an acute phase reactant. However, serum C-reactive protein (so named because it reacts with pneumococcal C-jK)lysaccharide) is measured. It binds with phospho-choline of pathogens, phospholipid constituents of damaged blood cells, and phagocytic cells, and it activates the complement system. All of the functions of C-reactive protein modulate inflammatory conditions of the body. These... 

Examples of Positive and Negative Acute Phase Proteins Positive... 

Negative acute phase proteins decrease during the acute phase response albumin appears to be a negative APP in all laboratory species, and sometimes decreases of transferrin and retinol-binding protein are observed. Plasma albumin falls in the acute phase response due to hemodilution, transfer into the extravascular space due to increased vascular permeability, increased colloidal osmotic pressure, and decreased synthesis. 

Vitamin A also has an important role in the differentiation of immune system cells, and mild deficiency, not severe enough to cause any disturbance of vision, leads to increased susceptibility to a variety of infectious diseases. At the same time, the synthesis of RBP is reduced in response to infection (it is a negative acute-phase protein), so that there is a reduction in the circulating concentration of the vitamin, and hence further impairment of immune responses. 

Plasma proteins are amphoteric molecules having both positive and negative charges that contribute to the balance of plasma ions and osmolality, particularly albumin. In cardiotoxicity, plasma protein patterns may be altered with increases of total protein, albumin, and acute phase proteins (e.g., myoglobin, C-reactive protein, and hbrinogen see Chapters 7 and 8). When proteins bind xenobiotics (or metabolites), their contributions to cation/anion balance may be altered. 

Katta Bolic was in a severe stage of negative nitrogen balance on admission, which was caused by both her malnourished state and her intra-abdominal infection complicated by sepsis. The physiologic response to her advanced catabolic status includes a degradation of muscle protein with the release of amino acids into the blood. This release is coupled with an increased uptake of amino acids for "acute phase" protein synthesis by the liver (systemic response) and other cells involved in the immune response to general and severe infection. 

Negative acute-phase reactant Chronic inflammatory or neoplastic diseases Protein-losing syndromes and malnutrition... 

Transthyretin levels are often used as an indicator of protein status because of its relatively short half-life, a high tryptophan content, a high proportion of essential-to-nonessential amino acids, and small pool size. However, it is a negative APR. Levels fall in inflammation and malignancy and in cirrhosis of the liver and protein-losing diseases of the gut or kidneys. Therefore a sensitive acute phase reactant, such as CRP, should always be assayed along with TTR if levels are to be used to estimate nutritional status. History and physical examination are also important aspects of such evaluations. ... 

Katta Bolic s severe negative nitrogen balance was caused by both her malnourished state and her intra-abdominal infection complicated by sepsis. The systemic and diverse responses the body makes to insults such as an acute febrile illness are termed the "acute phase response." An early event in this response is the stimulation of phagocytic activity (see Fig. 42.17). Stimulated macrophages release cytokines, which are regulatory proteins that stimulate the release of cortisol, insulin, and growth hormone. Cytokines also directly mediate the acute phase response of the liver and skeletal muscle to sepsis. 

The CCAAT/enhancer-binding proteins (C/EBP) are transactivators known for their involvement in the regulation of acute phase and inflammatory protein expression [106]. The family comprises several isoforms, which can homo- and heterodimerize through their basic leucine zipper region [107], or associate with other transcription factors, including NF-kB [108, 109]. Activation of the C/EBP proteins involves their phosphorylation in a negative regulatory domain [110, 111]. In a similar manner to PU.l, some C/EBP family... 

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