Interaction cellular, sensitivity

The cellular interaction of agonists depends on the physico-chemical nature and on the topographical distribution of the membrane receptors (62). Thus thrombin and PGE, mediated responses would depend on the number and the type (high affinity/low affinity) of receptors available for interaction with thrombin or PGE, respectively. The possibility diat platelets fiwrn SHR exhibit greater sensitivity to thrombin and PGE, because of differences in munber or affinity of their respective receptors has been examined by us (23,24). Hirombin as well as PGE, binding sites/platelets and dissociation constants have been found to be similar in WKY and SHR platelets (Fig.7, ref 23,24). Therefore, increased platelet reactivity to thrombin or PGE, is not attributable to changes in the number or the affinity of their respective receptors. 

One facile method for investigation of cellular interactions of liposomes, and more precisely, their ability to accumulate within cells, is the fluorescent microscopy. To meet this objective, liposomes are loaded with fluorescent marker (calcein or other suitable dye) at high concentration, whereby its fluorescence is self-quenched. Upon cellular fusion and internalization the dye is released from the carrier, diluted in the environment so the selfquenching effect is lost and the increased fluorescence is detected by fluorescent microscopy. In the case of effective cellular internalization of pH-sensitive liposomes, that is, without endosomal sequestration, calcein would have been diluted several-hundred-fold and the cells will display uniform cytosolic fluorescence. If the liposomes have been taken up by cells by endocytosis, punctuate fluorescence will be restricted to the secondary lysosomal and endocytic vacuoles. In contrast, adsorbed liposomes should... 

The sensitivity of cellular interactions to interfacial proteins probably is due to the presence of cell surface receptors for specific proteins and to the enhancement of receptor-protein interaction by the concentration of proteins at interfaces. To illustrate the role of specific proteins at interfaces,... 

Adsorbed proteins can greatly influence cellular reactions with synthetic materials. The sensitivity to adsorbed proteins, the variation in cellular response to specific proteins, and the rapid adsorption of proteins to all surfaces exposed to the biological environment, have led to the idea that the cellular response to implanted polymers is the result of specific interactions between components of the adsorbed protein layer on the polymer and the cell periphery. These observations, in turn, have led to the hypothesis that cellular interactions with foreign materials are controlled by the presence at the surface of specific proteins at sufficiently high surface density and degree of reactivity to elicit a response. Each of these factors constitutes an important aspect of the organization of the adsorbed protein layer. 

The extract dilution type of cell culture assay requires a solvent extraction of the biomaterial under consideration and testing of this extract, most commonly at various dilutions, for evidence of cytotoxicity and cellular interaction. This type of cell culture assay finds its most common use in providing information for regulatory compliance. As identified in the preceding Materials for Medical Devices section and in Table 1, low-molecular-weight extractables are of concern regarding biocompatibility. The extraction assay, carried out with a series of solvents that are hydrophilic and hydrophobic, permits examination of the potential cytotoxicity of extracts and the identification of materials within a biomaterial that may be cytotoxic. These types of assays ultimately permit identification and characterization of cytotoxic materials within biomaterials or the lack of cytotoxicity, as well as providing correlation with in vivo assays such as sensitization, irritation, intracutaneous (intradermal) reactivity, and other tests where the in vivo injection of extracts is required. 

This phenomenon, the killer factor, was discovered in S. cerevisiae but killer strains also exist in other yeast genera such as Hansemla, Candida, Kloeckem, Hanseniaspora, Pichia, Tom-lopsis, Kluyveromyces and Debaryomyces. Killer yeasts have been classified into 11 groups according to the sensitivity reaction between strains as well as the nature and properties of the toxins involved. The killer factor is a cellular interaction model mediated by the proteinic toxin excreted. It has given rise to much fundamental research (Tipper and Bostian, 1984 Young, 1987). Barre (1984, 1992), Radler (1988) and Van Vuuren and... 

Synthesis of the transferrin receptor (TfR) and that of ferritin are reciprocally linked to cellular iron content. Specific untranslated sequences of the mRNAs for both proteins (named iron response elements) interact with a cytosolic protein sensitive to variations in levels of cellular iron (iron-responsive element-binding protein). When iron levels are high, cells use stored ferritin mRNA to synthesize ferritin, and the TfR mRNA is degraded. In contrast, when iron levels are low, the TfR mRNA is stabilized and increased synthesis of receptors occurs, while ferritin mRNA is apparently stored in an inactive form. This is an important example of control of expression of proteins at the translational level. 

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