Publisher Summary

The primary role of the lungs is to facilitate the transfer of gases between the inspired air and the circulation, maintaining their concentration in the blood and tissues between the narrow limits essential for life. However, this is not their only function, because they are metabolically active. Like other organs, the lungs are under the control of the autonomic nervous system and have a complex innervation comprising adrenergic, cholinergic, and peptidergic components. Acting in concert with this pulmonary nervous system is a second regulatory mechanism, the pulmonary endocrine system. This internal system of endocrine control is mediated by a widely dispersed population of amine and peptide-secreting cells scattered among the epithelium of the airways from the trachea to the alveolar spaces; and constitute the pulmonary component of the diffuse endocrine system.

The lung as an endocrine organ

The primary role of the lungs is to facilitate the transfer of gases between the inspired air and the circulation, maintaining their concentration in the blood and tissues between the narrow limits essential for life. This is not, however, their only function, since they are metabolically highly active. For example, a number of their component tissues produce and metabolize derivatives of arachidonic acid, prostaglandins and leukotrienes, and the endothelium lining the pulmonary vessels is a particularly important site for the metabolism of many substances either generated there or arising elsewhere and passing through them (Becker, 1984). The most obvious example of this sort of activity is the conversion of angiotensin I to angiotensin II in endothelial caveolae (Biron, Campeau and David, 1969). In the sense that such substances act as chemical messengers and influence other tissues, the lung, in common with most other organs, could legitimately be said to possess an endocrine function.

Such activities are not, however, what this book is about. Like other organs, the lungs are under the control of the autonomic nervous system and have a complex innervation comprising adrenergic, cholinergic and peptidergic components (Barnes, 1987). Acting in concert with this pulmonary nervous system is a second regulatory mechanism, the pulmonary endocrine system. This internal system of endocrine control is mediated by a widely dispersed population of amine and peptide-secreting cells scattered amongst the epithelium of the airways from the trachea to the alveolar spaces and which constitutes the pulmonary component of the diffuse endocrine system described below. It is with the anatomy, physiology and pathology of this system of secretory cells and with the pulmonary tumours which follow its line of differentiation that this book is concerned.

Systems of control: the nervous, endocrine and immune systems

Homeostasis is maintained by the complex integration of a number of organ systems. Foremost in what has been implicitly seen as a hierarchy of control is the nervous system, with what might be called the ‘traditional’ endocrine system subserving a complementary role in maintaining homeostasis both directly, through its effects on metabolic processes, and indirectly, via its influence on other organs. The traditional endocrine system comprised a series of endocrine organs, the ‘ductless glands’, which controlled metabolic processes by secreting chemical messengers, or hormones (from the Greek hormao; ‘I set in motion’ or ‘stir up’) directly into the blood. These chemical messengers acted on specific target organs at a distance from their point of secretion. This system was considered to be separate from but to work in conjunction with the nervous system, the two acting together to control other bodily functions.

This simple concept has undergone continuous modification in the light of changing ideas about endocrinology and the relationship of the endocrine system to other systems of control. One such realization has been that the neural and endocrine systems are not merely complementary, but intimately related, structurally as well as functionally. This intimacy is typified by the integrated neural and endocrine mechanisms which operate in the hypothalamic–pituitary unit (Reichlin, 1981). Its recognition resulted not only in the emergence of the science of neuroendocrinology, but an appreciation that the nervous and endocrine systems had more in common than they had differences, that they represented two facets of a single integrated system. A further development supporting this view was the realization that populations of regulatory cells with many morphological and functional features in common with neurons could be identified within the tissues of all the major organ systems. Individually inconspicuous, but forming collectively an organ of considerable size, these populations of regulatory cells make up what has come to be known as the diffuse endocrine system.

A more recent conceptual move has been to include the immune system together with the nervous and endocrine systems as a third facet of a global control system (Harrison and Campbell, 1988). The cells of the immune system mediate immune and inflammatory responses by secreting peptides, the cytokines, and the peptides released from the cells of the pulmonary endocrine system might also be involved in such responses (Chapters 4 and 5). In addition, the sharing of certain antigens by cells of all three systems is increasingly described (Chapters 2, 7 and 10). It is possible even to visualize immune cells as circulating endocrine organs, mobile components of a combined neural, endocrine and immune system which work together to maintain homeostasis (Wolfe, 1991). Changing ideas about the inter-relationships of the nervous, endocrine and immune systems are illustrated in Figure 1.1.

Types of secretion

Central to the consideration of the neural, endocrine and immune systems as a unified control system is the fact that all their cells send out signals using chemical transmitters. The term endocrine comes from two Greek words, endon, meaning ‘within’ or ‘inner’ and krinein, meaning ‘to separate’ and denotes a process of internal, rather than external (exocrine) secretion, by means of which chemical messengers, hormones, are released from one cell to act upon another rather than into a duct. It is often stated that its use implies secretion into the circulation with a destined action at a distant site, but this is too narrow an interpretation in the light of the changing concepts outlined above. Whether a chemical messenger acts on the same cell as produces it (autocrine), on a contiguous cell as in the nervous system (neurotransmission and neuromodulation) on the cells in its immediate vicinity as in the diffuse endocrine system and during signalling between cells of the immune system (paracrine) or on a tissue some distance away as with the traditional endocrine organs, is essentially irrelevant (Figure 1.2). All involve internal (endocrine) secretion. If the process of secretion into the circulation needs to be denoted specifically, haemocrine would seem an appropriate term. Throughout this book, the term endocrine will be used to denote secretion of chemical messengers or hormones, irrespective of where they eventually act. The terms autocrine, paracrine and haemocrine will be used as defined above.

The diffuse endocrine system

The idea that organs like the gut and lung contain a system of cells which secrete chemical messengers and exert a local influence is not new. In 1870, Heidenhain described small yellow-brown cells in the epithelium of the canine intestine. Masson (1914) showed that they took up silver from solutions of its salts, the property of argentaffinity...