Ai-Antitrypsin

These proteins are called acute phase proteins (or reactants) and include C-reactive protein (CRP, so-named because it reacts with the C polysaccharide of pneumococci), ai-antitrypsin, haptoglobin, aj-acid glycoprotein, and fibrinogen. The elevations of the levels of these proteins vary from as little as 50% to as much as 1000-fold in the case of CRP. Their levels are also usually elevated during chronic inflammatory states and in patients with cancer. These proteins are believed to play a role in the body s response to inflammation. For example, C-reactive protein can stimulate the classic complement pathway, and ai-antitrypsin can neutralize certain proteases released during the acute inflammatory state. CRP is used as a marker of tissue injury, infection, and inflammation, and there is considerable interest in its use as a predictor of certain types of cardiovascular conditions secondary to atherosclerosis. Interleukin-1 (IL-1), a polypeptide released from mononuclear phagocytic cells, is the principal—but not the sole—stimulator of the synthesis of the majority of acute phase reactants by hepatocytes. Additional molecules such as IL-6 are involved, and they as well as IL-1 appear to work at the level of gene transcription. 

At present, severe ai-antitrypsin deficiency liver disease can be successfully treated by liver transplantation. In the future, introduction of the gene for normal ttj-antitrypsin into hepatocytes may become possible, but this would not stop production of the PiZ protein. Figure 50-7 is a scheme of the causation of this disease. 

In inflammatory conditions, activated PMNs may pro-teolytically (by release of lysosomal enzymes) and oxidatively (by release of HOCl) inactivate ai-antitrypsin. Studies of synovial fluid samples from patients with RA showed that a i-antitrypsin was both cleaved and oxidized, resulting in inactivation (Chidwick et al., 1991, 1994). Free-radical attack on ai-antitrypsin and its subsequent inactivation may contribute to the destruction of joint tissues in arthritis due to the imbalance between elastase and its inhibitors. 

Chidwick, K., Winyard, P.G., Zhang, Z., Farrell, A.J. and Blake, D.R, (1991). Inactivation of the elastase inhibitory activity of ai-antitrypsin in fresh samples of synovial fluid from patients with rheumatoid arthritis. Ann. Rheum. Dis. 50, 915-916. 

AP ai-antiproteinase also known as ai-antitrypsin and ai-proteinase inhibitor... 

As discussed in detail by Dillard et al. and by Mittman et al. the possible relationship of lysosomal proteases to chronic lung disease has been inferred from the finding of an increased incidence of emphysema in subjects deficient in serum ai>antitrypsin factor, an -globulin that can inhibit lysosomal proteases. (No effect of ozone on serum aj-antitrypsin inhibitor was noted in rabbits chronically exposed to ozone. ) Thus, an ozone-induced increase in concentrations of such enzymes in the lung might produce excess proteolysis and result in eventual chronic lung disease. However, the available evidence is inadequate to support the belief that such a process occurs in humans intermittently exposed to ozone. Further studies of this potential hazard would be of value. 

Antitrypsin (AAT). The ai-antitrypsin (AAT) level in serum is one of the nonspecific markers of the activity of various tumors. Studies discuss the importance of evaluation of the AAT level in CSF in patients with various CNS... 

Antitrypsin Blood and other body fluids contain a protein, ai -antitrypsin (ai-AT, currently also called ai-aritiproteinase), that inhibits a number of proteolytic enzymes (also called proteases or proteinases) that hydrolyze and destroy proteins. [Note The inhibitor was originally named oti-antitrypsin because it inhibits the activity of trypsin (a proteolytic enzyme synthesized as trypsinogen... 

J. N. Udall, K. J. Bloch, and W. A. Wtalker. Transport of proteases across neonatal intestine and development of liver disease In Infanta with ai-antitrypsin deficiency. 

Human plasma inhibits the hydrolysis of casein by stem bromeiain [76]. Stem tramelain is inhibited fay aj-macroglobiilin, but not by ai-antitrypsin [38,77]. 

The absorption of orally administered bromelain in humans was proven by means of measurement of proteolytic activities using the fluorogenic substrate Z-Arg-coumarin ana by immunopreciphaiion followed by electrophoresis and immunodetection. The results showed that orally administered bromelain is found In plasma of human volunteers at low, but clearly measurable, concentrations as a full-size proteolytically active protein. Die bromelain circulating in plasma appears to be partially bound to certain plasma proteins, two of which were identified as oc-macroglobulin and ai-antitrypsin [86],... 

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