Elastin and the Lung

Thorax: first published as 10.1136/thx.41.8.577 on 1 August 1986. Downloaded from Thorax 1986;41:577-585 Review article Elastin and the lung It is essential that the framework of all multicellular most prominently displayed in newly synthesised or organisms should include some materials with high juvenile elastin, is a glycoprotein that stains with ura- tensile strength and rigidity, such as bone and col- nyl acetate and leads, which appears as small fibrils lagen, to maintain shape and mechanical rigidity. In 10-12 nm in diameter concentrated around the addition, there is a requirement for a component with periphery of the amorphous elastin. The microfibrils intrinsic elasticity that can stretch and undergo elastic are chemically and morphologically quite distinct recoil when required. This property is supplied by an from the amorphous elastin. There is some evidence unusual fibrous protein, which over 150 years ago was to suggest that the microfibrils are secreted into the given the name elastin. extracellular matrix before elastin synthesis and func- Elastin fibres are present in virtually all vertebrate tion as a nucleation site for future elastin deposition. tissues, although it is only within a few, such as ar- For more details on every aspect of the microfibrils, teries, some ligaments, and the lung, that elastin com- readers are referred to other articles.24 prises an appreciable percentage of the total protein. The purification of elastin depends predominantly The ligamentum nuchae of grazing animals and the on its remarkable insolubility, even under harsh, aorta of most vertebrates contain over 50% elastin on denaturing conditions. The protein has been defined a dry weight basis. The elastin content of lungs on the operationally as the insoluble residue remaining after other hand is quite variable, ranging from as low as a tissue is autoclaved repeatedly or boiled in 01 N 2% in rodents up to 28% in the cow and in man. For NaOH for up to one hour. This procedure was satis- this reason most of the chemical and biological stud- factory for tissues comprised mostly of elastin and ies that have been conducted on elastin have used collagen. Isolation of a relatively intact and pure elas- either the bovine neck ligament or the ascending aorta tin is impossible using this method, however, in tis- of several species. Although the primary aim of this sues that have a low elastin content or are particularly article is to review the role and metabolism of elastin rich in glycoproteins or complex ground substance. In http://thorax.bmj.com/ in the lung, most of the background information must recent years milder yet considerably more complex come from elastin derived from other sources. The methods have been used. These methods have been findings may, however, be extrapolated to the lung, compared by Soskels and it is now fairly well since within a given species all elastins appear to be accepted that, even in such complex tissue as the lung, chemically the same, regardless of the tissue of origin. elastin can be purified in the absence of harsh alkali We may safely assume that the essentials of elastin extraction. "Pure" elastin, however, still remains as metabolism are the same in all tissues, although an operationally defined protein residue that has an apparently much influenced by other components in amino acid composition typical of elastin for that on October 2, 2021 by guest. Protected copyright. the extracellular matrix of that particular organ. particular species. This has created some confusion since with slight contamination this protein may Identification and purification of elastin appear as a different elastin. There have been reports of two distinct types of elastin within cartilage6 and The first century of elastin research was primarily synthesised by chick aorta in culture.7 Advanced directed towards the morphological and histological techniques analysing elastin messenger RNA do not features of the elastin fibre. This early history of elas- support this theory.89 Other studies have compared tin research has been reviewed in detail by Hass.' The the amino compositions of elastins derived from vari- elastin fibre is composed of two distinct components. ous organs within the same species. These studies The elastin, or amorphous component, is the major indicate that, once the glycoproteins and other pro- fraction, comprising some 90% of a mature fibre. It teins in close association with elastin have been com- derives its name from the absence of any repeating pletely removed, the compositions are the same structure or banding pattern, when reviewed under an within a species regardless of the tissue of origin.10l electron microscope. The microfibrillar component, Structure of elastin Address for reprint requests: Professor BC Starcher, Department of Biochemistry, University of Texas, Health Center at Tyler, PO Box The amino acid analysis of elastin is consistent with 2003, Tyler TX 75710, USA. its unique physical properties. Almost one third ofthe 577 Thorax: first published as 10.1136/thx.41.8.577 on 1 August 1986. Downloaded from 578 residues are glycine, about 12% are proline, and over sues that have been examined, including the lung, the 40% of the remaining amino acids contain hydro- data indicate that elastin synthesis is regulated by the phobic side chains, making this one of nature's most transcription and availability of mRNA .27 non-polar proteins. A survey of the amino acid com- Translation of the mRNAE produces a tropoelastin positions of elastin, from representative species of all molecule containing a short (24-26 residue) signal vertebrate classes and some invertebrate phyla, indi- peptide.8 As the chain elongation proceeds, select cates that elastin is present in all vertebrates except prolyl residues are hydroxylated by prolyl- Agnatha. " hydroxylase.8 '4 The hydroxylation of prolyl residues Renewed interest in elastin biochemistry began in in tropoelastin, unlike collagen, does not affect either the late 1950s and early 1960s with a series of inter- synthesis or stability of the molecule.28 29 Some esting nutritional observations on the effects of cop- investigators have even considered this a serendip- per deficiency in young growing animals, and the itous event that occurs simply because the machinery simultaneous studies on the chemistry of elastin and is present and the molecule resembles collagen in its crosslinks by the Cambridge group headed by many aspects of primary structure. The entire intra- Partridge.'2 13 The most dramatic signs of copper cellular elastin synthetic process requires about 20 deficiency are the fragmented appearance and consid- minutes.2' erable decrease in the amorphous elastin content of Tropoelastin is secreted from the cell into the major blood vessels, leading to aortic aneurysms and extracellular matrix as a protein with a molecular subsequent death of the animal.'4 It soon became weight of 72000. As tropoelastin molecules become apparent that lysyl oxidase, a copper metalloenzyme, aligned, perhaps in association with the microfibrils, was required for the formation of crosslinkages that hydrophobic interactions occur, presumably leading stabilise the elastin fibre.'5 In the absence of cross- to coacervation. Lysyl oxidase subsequently converts linking, a soluble, non-functional elastin molecule the epsilon (E) aminos of all but five or six of the total accumulates in the tissues in sufficient quantities for it 37 lysine residues in tropoelastin to aldehydes. These to be isolated. This rather fortunate event (for the very reactive residues (allysines) spontaneously con- biochemist) has led to the characterisation of tro- dense to form various Schiff base and aldol conden- poelastin, the soluble monomer form of elastin, which sation crosslinks. Within a few days most of the cross- has now been isolated from several tissues, including links have isomerised into the stable quaternary ligaments, aortas, and lungs.16 Tropoelastin has been pyridinium ring structures of desmosine and iso- essential for the sequencing of this otherwise highly desmosine. Several excellent reviews have discussed http://thorax.bmj.com/ crosslinked and very difficult protein. Characteristic the crosslinking process in great detail.30 31 repeating sequences are found throughout the tro- Lysyl oxidase has been isolated from several poelastin molecule. The sequences ala-ala-ala-lys and sources and, although shown to be present in the ala-ala-lys each repeat six times and are believed to be lung, it has not been isolated from that tissue. Copper the sites for future oxidation by lysyl oxidase and sub- is required for enzymatic activity, which explains the sequent crosslink formation.17 Several hydrophobic connective tissue defects observed in copper deficient repeat sequences are also found in elastin, including animals. Additionally, lathrogens like BAPN inhibit the pentapeptide pro-gly-val-gly-val and a hexa- the enzyme, producing the connective tissue defects peptide pro-gly-cal-gly-val-ala. Some have proposed that are seen in copper deficiency. 4 Genetic disorders on October 2, 2021 by guest. Protected copyright. that the pentapeptide repeats form a /B spiral structure have also been described that are characterised by low consisting of / turns while the crosslinked regions lysyl oxidase activity and severe connective tissue form a more rigid a helical conformation. Other defects. 14 31 sharply contrasting views, derived from physical mea- Once the tropoelastin molecules are crosslinked

Load more