Hyaluronan in respiratory injury and repair
Hyaluronan in respiratory injury and repair
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DOI：
10.1164/rccm.200205-449pp
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发表时间：
2003-05-01
影响因子：
24.7
通讯作者：
Cantor, JO
中科院分区：
文献类型：
--
作者：
Turino, GM;Cantor, JO
Over the past two decades, much of the research on the cellular hyaluronic acid as the terminology. HA is a naturally occurring, and biochemical reactions to injurious agents of the lung has linear polysaccharide with repeating disaccharide units comfocused on specific cells and cytokines and their appearance or posed of glucuronic acid and N-acetyl glucosamine. Both monodisappearance in the alveolar milieu. Little emphasis has been saccharides have the-D-anomeric configuration of C-1. The given to the connective tissue matrix itself, in which specific re- linkage from the glucuronic acid to N-acetyl glucosamine is (1→ sponses take place. Early on, the underlying premise was that the 3), and the linkage from N-acetyl glucosamine to glucuronic acid matrix substances such as glycosaminoglycans and the fibrous is (1→ 4)(Figure 1). structure of the lung related to collagen and elastin are function- HA belongs to a family of structurally similar polysaccharides ally relatively unresponsive and structurally fixed. This is far from called glycosaminoglycans, which includes hyaluronan, chontrue, and a primary purpose of this “perspective” is to describe droitin sulfate, dermatan sulfate, keratan sulfate, heparan sulthe dynamic nature of the constituents of the interstitial space. fate, and heparin. These polysaccharides all contain repeating The pulmonary matrix, with its cellular constituents and fluc- disaccharide units that are characterized by 1-amino sugar and tuating cytokines, should more realistically be considered as at least one negatively charged group of carboxylate or sulfate. an integrated, interactive unit rather than separate unrelated Hyaluronan differs from the other glycosaminoglycans in that entities. Also, it is becoming more apparent that the integrity it does not contain sulfur. and balance of matrix components themselves, which undergo A unique characteristic of HA, which relates to its variable degradation and reconstruction, are essential for normal lung functions, is its hydration. HA exists in solution in a flexible, function and the response to injury (1). coiled configuration (5–6), which is well hydrated and contains In recent years, new insights have been gained into the func- approximately 1000-fold more water than polymer (6). Also, tional role of matrix components per se, modulating injury to the molecular weight of HA varies in specific tissues. Normal the pulmonary structure and altering function. One of the com- synovial fluid has HA of an average of 7,000 kD (7). In cartilage ponents that has received increasing study in the last decades is and lung, it has 2,000 (8) and 220 kD (9), respectively. hyaluronic acid (HA)(2). Since the discovery of HA in 1934 by The concentration of HA in a tissue can determine its water Dr. Karl Meyer (3), voluminous literature has evolved from both content. This relationship has been demonstrated for normal basic and clinical studies. For the purposes of this review, HA animal lungs, where reductions in lung HA induced by hyaluroniwill be considered from five aspects:(1) the chemical characteris- dase have been directly correlated with reductions in the extratics of HA,(2) HA in embryogenesis and response to injury, vascular lung water volume (10). This correlation has also been (3) binding proteins and receptors,(4) molecular size and the demonstrated in experimental alveolitis (9). effect on biologic function, and (5) HA in respiratory disease. This perspective, it is hoped, will indicate the extraordinary
