Proliferation and differentiation in mammalian airway epithelium

Abstract

The proliferative potential of the various cell types present in airway epithelium have been described. The techniques used to assess their proliferative activity (MI and LI), growth fraction and length of each phase of the cell cycle have been given in outline. By use of a variety of techniques, there is ample capacity to recruit non-cycling cells rapidly into the cell cycle. Under certain circumstances (e.g. cigarette smoke exposure and mechanical trauma) the mucous (goblet) cell is proliferative and its role in epithelial repair has been clearly underestimated. Factors contributing to the variation seen in baseline proliferation include species, sex, hormonal status, airway level, age, diurnal rhythm and pathogen-free status. A variety of stimuli increase proliferation as part of a reparative process: 1) irritation by oxidants, chemical carcinogens or enzymes, 2) mechanical injury, 3) infection and 4) certain drugs, some of which stimulate division whilst others inhibit the proliferative response to irritation and may be useful in controlling the response. Increases in the numbers of some cell types may be due to differentiation rather than proliferation and the 3-compartment model can be applied to airway epithelium comprising: 1) the self renewing/proliferating compartment, made up of basal and secretory cells in the large airways, nonciliated bronchiolar (Clara) cells in the small airways, and type II cells in the alveolus; 2) the differentiation compartment containing mature functional cells, some of which retain the capacity to divide, e.g. serous, mucous (goblet), Clara, type II cells; 3) the fully-mature end stage cells (e.g. ciliated cells) which do not normally divide. The nervous system and lymphocytes present in epithelium and bronchus-associated lymphoid tissue may also have a part to play in controlling cell division and their roles should be investigated further. However, the lung remains relatively unexplored with regard to the factors which control the proliferation and differentiation of its many distinct cell types, both in health and disease.