Plasma proteins antibodies

Proteins that enable the cell to perform special functions within the organism, e.g., hemoglobin, muscle proteins, storage proteins, cilial proteins and exoproteins, such as collagen blood plasma proteins, antibodies, milk proteins, and proteohormones, structural and regulatory proteins required for the specialized function of the cell, etc. 

The fundamental role of blood in the maintenance of homeostasis and the ease with which blood can be obtained have meant that the study of its constituents has been of central importance in the development of biochemistry and clinical biochemistry. The basic properties of a number of plasma proteins, including the immunoglobulins (antibodies), are described in this chapter. Changes in the amounts of various plasma proteins and immunoglobulins occur in many diseases and can be monitored by electrophoresis or other suitable procedures. As indicated in an earlier chapter, alterations of the activities of certain enzymes found in plasma are of diagnostic use in a number of pathologic conditions. 

The concentration of total protein in human plasma is approximately 7.0-7.5 g/dL and comprises the major part of the solids of the plasma. The proteins of the plasma are actually a complex mixture that includes not only simple proteins but also conjugated proteins such as glycoproteins and various types of lipoproteins. Thousands of antibodies are present in human plasma, though the amount of any one antibody is usually quite low under normal circumstances. The relative dimensions and molecular masses of some of the most important plasma proteins are shown in Figure 50-1. 

The preparation of antibodies specific for the individual plasma proteins has greatly facilitated their smdy, allowing the precipitation and isolation of pure proteins from the complex mixmre present in tissues or plasma. In addition, the use of isotopes has made possible the determination of their pathways of biosynthesis and of their turnover rates in plasma. 

Immunoglobulins are associated with the y-globulin fraction of plasma proteins but, as stated earlier, not all immunoglobulins exhibit antibody activity. 

The complement system comprises twenty plasma proteins present in the blood and in most bodily fluids. They are normally present in an inactive form but become activated via two separate pathways the classical pathway, which requires antibody, and the alternative pathway, which does not. Once the initial components of complement are activated, a cascade reac-... 

Numerous problems in the construction of chnically applicable drug targeting moieties still need to be solved. Of these issues, immunogenicity after repeated administration, counterproductive hver clearance, and production 5delds are the most important. Although the problem of immunogenicity is beheved to have been solved for monoclonal antibody therapy by the development of humanized and fully human antibodies [110], for other carrier systems such as modified plasma proteins and peptide modified polymers, this remains an important issue. 

Antibodies, with half-lives measured in days, are among the most stable natural proteins, far more stable than larger proteins (MW > 150kDa), which have half-lives measured in minutes or seconds. Indeed, the stability of IgG is comparable to the best-conserved major plasma protein, serum albumin (Table 10.2). 

Plasma. Normal blood plasma is a clear, slightly yellowish fluid, which is approximately 55% of the total volume of the blood. The plasma is a water solution in which are transported the digested food materials from rhe walls of the small intestine to the body tissues, as well as the waste materials from the tissues to the kidneys. Consequently, this solution contains several hundred different substances. In addition, the plasma carries antibodies, which are responsible for immunity to disease, and hormones. The plasma transports most of the waste carbon dioxide from the tissues back to the lungs. Plasma consists of about 91% water, 7% piotein material, and 0.9% various mineial salts, The icmaindei consists of substances already mentioned. The salts and proteins are important in keeping the proper balance between the water in the tissues and in the blood, Disturbances in this ratio may result in excessive water in the tissues (swelling or edema). The mineral salts in the plasma all serve... 

GLOBULINS. Proteins that are insoluble in water, but that dissolve readily in aqueous salt solutions. The term globulins is applied to cenain subgroups of the plasma proteins. See also Antibody and Blood. 

Size measurements can be done to study the interaction of polymeric micelles with biological media (Jones and Leroux, 1999). For instance, PERP -bPEO micelles were found to maintain their initial size in the presence of antibodies and bovine serum albumin, suggesting the apparent absence of interaction with plasma proteins (Kabanov et al., 1992). 

Boado et al. [28] devised delivery systems based on conjugates of streptavidin and the 0X26 monoclonal antibody directed to the transferrin receptor as a carrier for the transport of ASO. These delivery systems were found to transport peptide nucleic acid antisense molecules, but not ASO, across the BBB. These authors attributed this difference to preferential binding of phosphorothioate oligonucleotide to plasma protein instead of the antibody complex, which reduced their transport. 

Protein solution (protein, antibody) Depending on the estimated strength of binding, 10 to 0.1 p,g/mL corresponding to a dilution of 1 100 to 1 10,000 for a concentration of stock solution of 1.0 mg/mL (see Note 2). For a lower estimated affinity a higher concentration of the protein should be used. For protein mixtures (blood, plasma, cell extracts, etc.) estimation of the content of the target protein is necessary. 

ApoSAA, normally a trace component of plasma, is an acute-phase plasma protein, that is, one that is elevated in a variety of disease states (R18). Its identification is interesting. A small protein of 76 residues, now called protein AA, was identified during the study of the proteins present in extracellular amyloid deposits in the type of amyloidosis particularly associated with inflammation (B24, H36, Lll, S38), Antibodies to protein AA reacted with two AA-related proteins in plasma, one of approximate Mr 180,000 (SAA) and the other found in HDL of Mr 14,000-15,000 or 12,000 (apoSAA) (A19, B25, B26, L12, L15). The N-terminal 76-amino-acid portion of apoSAA is identical to that of amyloid protein AA (E8). Human apoSAA has now been sequenced and has been shown to consist of 104 amino acid residues (B27). Further studies in man have demonstrated microheterogeneity in apoSAA (B18, B19, M30) and Benditt et al. describe specific amino acid substitutions (B27, P6). Shore et al. have described a second similar threonine-poor apolipoprotein, apparently a dimer of Mr 40,000... 

Figure 5. Undesirable staining of plasma proteins with antibody to kappa light chain. Plasma cells stain specifically.

---