We describe a class ofcationic structural proteins that associate specifically with intermediate filaments (IF) but not with other types ofcytoskeletal proteins. These proteins, for which the term filaggrin is introduced, are isolated from the stratum corneum of mammalian epidermis. They are species-distinct proteins; for example, rat and mouse filaggrin have different molecular weights and amino acid compositions, but are nevertheless chemically and functionally very similar. They interact in vitro with the IF of several different types of cells to form large fibers or macrofibrils in which many IF are highly aligned in parallel arrays. Stoichiometric analyses suggest that two molecules offilaggrin bind to each three-chain building block of the IF, possibly by ionic interactions with the coiled-coil et-helical regions of the IF.Intermediate filaments (IF) are ubiquitous constituents of the cytoskeleton of eukaryote cells. However, detailed studies of the IF isolated from a wide variety ofdifferent types ofcells have indicated broad differences in their solubility and immunological properties and in the size and complexity of their constituent subunits (1-3). Nevertheless, the IF studied to date appear to be structurally analogous. They are all a-type fibrous proteins and are composed of a common three-chain building block (4-7).Mammalian epidermis is unusual in that its principal differentiation products are filaments of the IF type (keratin filaments). These are synthesized and deposited intracellularly in the inner living cell layers as bundles or fibrils and eventually form the bulk ofthe terminally differentiated cells ofthe stratum corneum (8). The epidermis also produces significant amounts of another structural protein, which has distinctly different physicochemical properties from the IF. This protein is synthesized in the granular layer as a highly phosphorylated precursor and accumulates in amorphous keratohyalin granules, but it is dephosphorylated to become highly cationic when the granular cells differentiate to form the stratum corneum cells (9). The rat cationic protein, called stratum corneum basic protein (10), histidine-rich protein II (11), or histidine-rich basic protein (12), is thought to function in the stratum corneum as an interfilamentous matrix and thereby contribute to the formation ofthe characteristically insoluble protein complex ofthe epidermis, keratin. Support for this notion has been adduced from experiments in vitro. Mixing ofepidermal keratin IF with the rat cationic protein results in the formation of insoluble fibrous structures, or macrofibrils (12)(13)(14)(15). These macrofibrils consist of large numbers of keratin IF aligned in parallel arrays reminiscent of the keratin fibrils in the stratum corneum.In this paper, we report the isolation and characterization of a functionally similar although chemically distinct protein from mouse epidermis. Both the rat and mouse cationic proteins form macrofibrils when mixed with epidermal and inner root sheath keratin IF a...

No abstract

1139 pyrimidine monoadducts, by subsequent light irradiation.'The conversion of psoralen DNA-monoadducts to DNA-crosslinks is not without potential problems. For some as yet unknown period of time photosensitised skin may continue to be further damaged by exposure to either direct or indirect sunlight as the conversion of monoadducts to crosslinks occur. Physicians would be well advised to realise that the cessation of black light irradiation is not the end of the treatment unless the lesions are kept in the dark, perhaps for several weeks.

Soluble cyclic GMP-phosphodiesterase was measured in normal and psoriatic epidermis. The specific activity of the enzyme was increased almost four-fold in involved compared with normal epidermis, and two- to three-fold in involved compared with uninvolved epidermis. The enzyme activity from all three sources was inhibited by 40-50% by ethylene glycol tetraacetic acid (EGTA). These results indicate that in addition to the reported enhanced capacity of psoriatic epidermis to generate cGMP, it has an increased ability to hydrolyse this nucleotide, although to a lesser degree than the augmentation found in soluble guanylate activity from psoriatic epidermis. These observations are compatible with the elevated steady-state levels of this nucleotide observed in the involved epidermis of psoriasis.

A 54-year-old man had severe psoriasis with associated arthritis for 10 years. Attempts at therapy with tars, topical steroids and a short course of ultraviolet light were unsuccessful. His psoriasis cleared 6 weeks after cardiac surgery requiring cadiopulmonary bypass oxygenation.