D

Figure 2 Haptenation of cells and extracellular molecules by molecules with little or no intrinsic reactivity. Metabolism of drugs (occurring primarily within hepatocytes, keratinocytes and other cells) can create reactive intermediates that can form covalent linkages to carrier molecules. Haptenation of molecules being synthesized in the cell at the time of drug metabolism can result in long-lasting surface expression of haptenated molecules and secretion of univalent and multivalent carriers. Reactive metabolites also may escape to the extracellular space to haptenate any suitable carrier.

Figure 2 Haptenation of cells and extracellular molecules by molecules with little or no intrinsic reactivity. Metabolism of drugs (occurring primarily within hepatocytes, keratinocytes and other cells) can create reactive intermediates that can form covalent linkages to carrier molecules. Haptenation of molecules being synthesized in the cell at the time of drug metabolism can result in long-lasting surface expression of haptenated molecules and secretion of univalent and multivalent carriers. Reactive metabolites also may escape to the extracellular space to haptenate any suitable carrier.

haptenation (Figure 1). Cell surfaces, extracellular structural proteins and diverse soluble molecules become haptenated. Approximately 10% of the penicillin molecules administered become covalentlv bound to human cells, proteins and other body constituents. Individual cells can accumulate thousands of surface hapten determinants within minutes of exposure to therapeutic concentrations of (3-lactam antibiotics.

Most low molecular weight substances used in clinical medicine are not reactive with macromol-ecules. As depicted in Figure 2, however, metabolites of some medications can haptenate. Intracellular haptenation of proteins being synthesized at the time of drug exposure can lead to haptenation of molecules eventually expressed on the cell surface, or to release of haptenated cellular secretion products. Extracellular metabolism or release of reactive intermediates into the extracellular space also can lead to cell surface haptenation and haptenation of fixed and soluble extracellular molecules.

Thus, the generation of immunogenic haptens and of targets for immunopathologic reactions occurs by diverse pathways. A dynamic array of haptenated cell surfaces, haptenated fixed proteins such as collagen, soluble molecules bearing single hapten sub-stituents (univalent carriers), and soluble molecules bearing multiple hapten substituents (multivalent carriers) appears during drug therapy.

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