Plasma protein materials

Materials may be absorbed by a variety of mechanisms. Depending on the nature of the material and the site of absorption, there may be passive diffusion, filtration processes, faciHtated diffusion, active transport and the formation of microvesicles for the cell membrane (pinocytosis) (61). EoUowing absorption, materials are transported in the circulation either free or bound to constituents such as plasma proteins or blood cells. The degree of binding of the absorbed material may influence the availabiHty of the material to tissue, or limit its elimination from the body (excretion). After passing from plasma to tissues, materials may have a variety of effects and fates, including no effect on the tissue, production of injury, biochemical conversion (metaboli2ed or biotransformed), or excretion (eg, from liver and kidney). 

Biomedical Applications Due to their excellent blood compatibility (low interaction with plasma proteins) and high oxygen and moisture permeabilities, siloxane containing copolymers and networks have been extensively evaluated and used in the construction of blood contacting devices and contact lenses 376). Depending on the actual use, the desired mechanical properties of these materials are usually achieved by careful design and selection of the organic component in the copolymers. 

Table 50-2 summarizes the functions of many of the plasma proteins. The remainder of the material in this chapter presents basic information regarding selected plasma proteins albumin, haptoglobin, transferrin, ceruloplasmin, aj-antitrypsin, aj i roglobulin, the immunoglobulins, and the complement system. The lipoproteins are discussed in Chapter 25. 

The fluid portion of the blood, the plasma, accounts for 55 to 60% of total blood volume and is about 90% water. The remaining 10% contains proteins (8%) and other substances (2%) including hormones, enzymes, nutrient molecules, gases, electrolytes, and excretory products. All of these substances are dissolved in the plasma (e.g., oxygen) or are colloidal materials (dispersed solute materials that do not precipitate out, e.g., proteins). The three major plasma proteins include ... 

Protein Binding. The degree to which a chemical binds to plasma proteins will highly influence its distribution. Albumin, the most prominent of the many proteins found in mammalian plasma, carries both positive and negative charges with which a polar compound can associate by electrostatic attraction. As with all such reactions, it can be described by the following equations. The more avidly bound the material, the less will be distributed to surrounding fluids as part of a solution and only that portion that is free in solution will be available for diffusion into the tissues. 

Materials Required Plasma protein solution 2.0 ml mixed phosphate buffer pH 7.0 with azide [To 1000 ml of a solution containing 1.8% w/v of disodium hydrogen orthophosphate and 2.3% w/v of sodium chloride and sufficient of a solution containing 0.78% w/v of sodium dihydrogen orthophosphate and 2.3% w/v of sodium chloride (about 280 ml) to produce a pH of 7.0 Dissolve sufficient sodium azide in the resulting solution to give a 0.02% w/v solution] 1000 ml ... 

It must be mentioned here that some of the results discussed in Sect. 4.3 were obtained with cell suspensions in Hanks -balanced salt solution (HBSS) in the absence of plasma proteins. The present author believes that the random-network concept can be applied to the events which happen to lymphocytes, platelets or erythrocytes when they come into direct contact with hydrated material surfaces in the absence of interventing protein. 

The packing material first described for direct injection of biological samples was prepared by simply saturating the accessible adsorption sites of a Cis reversed-phase silica with human plasma proteins (105). After saturation, the human plasma proteins were denatured at the external surface, and their native conformation was destroyed. With this treatment, the proteins formed a hydrophilic layer with weak ion-exchange properties, which provided protection from contact with the sample proteins, whereas the alkyl ligands inside the pores remained unchanged and thus served for analyte retention. The retention behavior of the saturated phase did not alter with this treatment, but the efficiency was reduced dramatically. Such protein-coated columns have shown a lifetime of several months (106). 

Fig. 6.2. Model for how FcRn rescues IgG from catabolism by recycling and transcytosis. IgG and many other soluble proteins are present in extracellular fluids. Vascular endothelial cells are active in fluid phase endocytosis of blood proteins. Material taken up by these cells enters the endosomes where FcRn is found as an integral membrane protein. The IgG then binds FcRn in this acidic environment. This binding results in transport of the IgG to the apical plasma membrane for recycling into the circulation, or to the basolateral membrane for transcytosis into the extracellular space. Exposure to a neutral pFI in both locations then results in the release of IgG. The remaining soluble proteins are channeled to the lysosomal degradation pathway.

The most frequently studied clinically relevant material has been blood plasma. Although the estimated contributions of the main antioxidants obtained by different authors for various methods of assay differ to some extent, it is clear uric acid is the main determinant of TAC of human blood plasma (Table 6), the next being plasma protein (mainly thiol groups of the proteins). In deproteinized plasma, TAC showed a 99% correlation with urate (M14). It has been reported that about 30% of... 

Specific domains of proteins (for example, those mentioned in the section Organic Phase ) adsorbed to biomaterial surfaces interact with select cell membrane receptors (Fig. 8) accessibility of adhesive domains (such as specific amino acid sequences) of select adsorbed proteins may either enhance or inhibit subsequent cell (such as osteoblast) attachment (Schakenraad, 1996). Several studies have provided evidence that properties (such as chemistry, charge, and topography) of biomaterial surfaces dictate select interactions (such as type, concentration, and conformation or bioactivity) of plasma proteins (Sinha and Tuan, 1996 Horbett, 1993 Horbett, 1996 Brunette, 1988 Davies, 1988 Luck et al., 1998 Curtis and Wilkinson, 1997). Albumin has been the protein of choice in protein-adsorption investigations because of availability, low cost (compared to other proteins contained in serum), and, most importantly, well-documented conformation or bioactive structure (Horbett, 1993) recently, however, a number of research groups have started to examine protein (such as fibronectin and vitronectin) interactions with material surfaces that are more pertinent to subsequent cell adhesion (Luck et al., 1998 Degasne et al., 1999 Dalton et al., 1995 Lopes et al., 1999). 

Horbett, T. A., Frinciples underlying the role of adsorbed plasma proteins in blood interactions with foreign materials. Cardiovasc. Pathol. 2,137S-148S (1993). 

Particles introduced into the bloodstream are covered rapidly by components of the circulation, such as plasma proteins, in a process called opsonization. Opsonization makes the particles recognizable to the body s major defense system, the reticuloendothelial system (RES). The RES comprises a diffuse system of phagocytic cells (which engulf inert material) that are primarily associated with the connective tissues in the liver, spleen, and lymph nodes. Macrophage (Kupffer) cells in the liver and macrophages of the spleen and circulation are important in removing particles identified by opsonization. A significant fraction of nanoparticles can be cleared from the circulation system in as little as 15 minutes [48, 49],... 

The only other known study on the binding of A9-tetrahydrocannabinol to plasma proteins was performed with electrophoretic techniques on tritium-labeled material and human plasma (14). The compound was 90 -95% associated with lipoproteins. 

Naturally occurring peptides, typically below the kidney size cut-off and, hence, usually collected from urine or from blood hemodialysate, provide a complementary picture of many events at the low-mass end of the plasma proteome. It provides a large source of proteins and peptides below 45 kDa. Such material has been analyzed by combined chromatography and MS approaches to resolve -5000 different peptides, including fragments of 75 different proteins [60]. Of the fragments, 55% percent were derived from plasma proteins, and 7% of the entries represented peptide hormones, growth factors, and cytokines. 

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