Protease plasma

Homo sapiens (compared to Drosophila melanogaster) Large-scale gene duplications with substantial expansion of genes involved in acquired immune response (B cells, T cells, major histocompatibility complex genes, cytokines, chemokines and their receptors), plasma proteases (complement and hemostatic proteins), proteins associated with apoptotic regulation and proteins related to neuronal network formation and electrical coupling... 

Pharmacokinetics Inactivated by endogenous plasma protease inhibitors. Clearance occurs within 2 hr of initiating infusion. Half-life 1.6 hr. 

Since a major component of all cells is protein, proteases could be very destructive if they were not carefully controlled or compartmentalized. The potential seriousness of uncontrolled proteolysis can be recognized by the fact that ca. 10% of the proteins by weight found in human plasma are protease inhibitors. The currently recognized plasma protease inhibitors are listed in Table I (3,4). In addition to the plasma inhibitors, there are other inhibitors that are more localized and have not been as well characterized. 

G22. Gravagna, P., Gianazza, E., Arnaud, P., Neels, M., and Ades, E. W., Modulation of the immune response by plasma protease inhibitors. II. Alpha 2-macroglobulin subunits inhibit natural killer cell cytotoxicity and antibody-dependent cell-mediated cytotoxicity. Scand. J. Immunol. 15, 115-118 (1982). 

Dickinson AM, Shenton BK, Alomran AH, Donnelly PK, Proctor SJ. Inhibition of natural killing and antibody-dependent cell-mediated cytotoxicity by the plasma protease inhibitor alpha 2-macroglobulin (alpha 2M) and alpha 2M protease complexes. Clin Immunol Immunopathol 1985 36 259-5. 

Figure 20-7 Overview of the complement cascades. Activation via the classical pathway is shown on the left and via the alternative pathway on the right. Continuous tickover by hydrolysis of C3 to C3i is shown at the center top. Direct activation of C3 by neutrophil and plasma proteases also may occur.The control mechanisms are shaded. (Courtesy j.W. Whicher, with modifications.)...

To obtain the maximum rate of renin activity, saturating amounts of the renin substrate, angiotensinogen, should be present in the reaction system. In most procedures, however, the only substrate provided is that present in the test plasma, and its concentration can be quite variable. According to some investigators, PRA is best estimated when the plasma specimen is incubated with an excess of exogenous renin substrate prepared from nephrectomized human subjects, oxen, or sheep. This type of assay is usually known as a plasma renin concentration assay rather than PRA assay. Unfortunately the measured renin depends on the source and concentration of the renin substrate. Synthetic peptides that resemble the M-terminal portion of angiotensinogen have also been used as renin substrates, but these substances can be hydrolyzed by nonspecific plasma proteases. 

The discipline has progressed considerably since then, although some of the limitations (immunogenicity and targeting) still exist. The advent of recombinant DNA technology, cloning, and wide-scale enzyme purification have basically solved the first problem. Our laboratory and several others [21-28] have demonstrated clearly that enzymes can be modified so as to dramatically improve on their resistance to biodegradation or stability at 37°C or in the face of a host of different plasma proteases. The problem of animal models has also been partly... 

An RIA using a rabbit heteroantiserum was the most sensitive and was capable of detecting as little as I pg of FTS, allowing for the quantitation of FTS in human peripheral blood. However, in order to detect FTS in serum it was first necessary to filter all specimens through an Amicon GF-50A membrane to remove large plasma proteases that would otherwise degrade the molecule. However, such a procedure could also remove any thymulin... 

On considering that liberation of the C-kinin in the serum of HANE patients was blocked by soybean trypsin inhibitor and EACA, compounds which do not inhibit Cls, another plasma protease, such as plasma kal-likrein or plasmin, appeared to be involved in the liberation of the C-kinin (Nilsson et al., 1966 Lundh et aL, 1968 Sheffer et al., 1972). Furthermore, the disease responds to treatment with the plasmin inhibitors trasylol and EACA (Sheffer et al., 1972 Frank et al., 1972). 

H. Lack, Staphyloklnase An Activator of Plasma Protease, Nature, 161 559-560 (1948). 

Another abundant plasma protease inhibitor, ai-antiprotease (apantitrypsin), irreversibly inhibits neutrophil elastase by forming an enzyme-inhibitor complex (38). Levels of complexed forms of ai-antiprotease are significantly increased in chronic wound fluids and at least some of these complexes contain elastase (13,22). 

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