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Crosstalk between autoreactive T cells and alveolar type II epithelial cells in inflammation and tolerance

von Dr. Marcus Gereke

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[1.] Mag/Fragment 009 04 - Diskussion
Zuletzt bearbeitet: 2014-03-15 12:43:36 Graf Isolan
BauernOpfer, Fragment, Gesichtet, Knight and Holgate 2003, Mag, SMWFragment, Schutzlevel sysop

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Untersuchte Arbeit:
Seite: 9, Zeilen: 4-33
Quelle: Knight and Holgate 2003
Seite(n): 432, 433, Zeilen: 432: 12-13, last para - 433: l.col: 1ff
The epithelium constitutes the interface between the internal milieu and the external environment, and as such, it is the first point of contact for inhaled substances, in particular, respiratory viruses, airborne allergens, and environmental pollutants, as well as being a primary target for inhaled respiratory drugs (Folkerts et al., 1998; Gizycki et al., 1997).

At least eight morphologically distinct epithelial cell types are present in human respiratory epithelium, which can be classified in three different categories: basal, ciliated and secretory epithelial cells (Spina, 1998). Columnar ciliated epithelial cells are the predominant cell type within the airways, constituting more than 50% of all epithelial cells (Spina, 1998). The primary role of the ciliated apical surface is highlighted by the directional transport of mucus from the lung to the throat (Harkema et al., 1991). Mucus cells (goblet cells) are responsible for the control of the correct amount of mucus and the viscoelasticity of mucus for efficient mucociliary clearance by releasing acid mucins from their granules. These cells are thought to be capable of self-renewal and may also differentiate into ciliated epithelial cells (Evans et al., 1988; Harkema et al., 1991). Serous cells are also secreting cells and produce neutral mucin and a yet unidentified non-mucoid substance (Knight and Holgate, 2003). Basal cells are ubiquitous in the conducting epithelium, although the number of these cells decreases with airway size and the increasing thickness of the basal cell layer correlates with increasing size of the airway (Evans et al., 1988; Evans et al., 1990). Similar to the skin, the basal cell is thought to be the primary stem cell, giving rise to the mucus and ciliated epithelial cells. In smaller airways, where basal cells are sparse or absent, Clara cells perform the primary stem cell role.

In addition to their progenitor and structural roles, basal cells are also thought to secrete a number of bioactive molecules including neutral endopeptidase, 15-lipoxygenase products and cytokines (Knight and Holgate, 2003). In humans, Clara cells are located in large (bronchial) and small (bronchiolar) airways. The cells produce bronchiolar surfactant and are also characterized by agranular endoplasmic reticulum in the apical cytoplasm and granular endoplasmatic reticulum basally. In addition to their role in secretion, Clara cells are believed to metabolize xenobiotic [compounds by the action of p450 mono-oxygenases and may also produce specific antiproteases such as secretory leukocyte protease inhibitor (De Water et al., 1986).]


De Water R, Willems LN, Van Muijen GN, Franken C, Fransen JA, Dijkman JH, Kramps JA. Ultrastructural localization of bronchial antileukoprotease in central and peripheral human airways by a gold-labeling technique using monoclonal antibodies. Am Rev Respir Dis. 1986 May; 133 (5): 882-90.

Evans MJ, Plopper CG. The role of basal cells in adhesion of columnar epithelium to airway basement membrane. Am Rev Respir Dis. 1988 Aug; 138 (2): 481-3.

Evans MJ, Cox RA, Shami SG, Plopper CG. Junctional adhesion mechanisms in airway basal cells. Am J Respir Cell Mol Biol. 1990 Oct; 3 (4): 341-7.

Folkerts G, Nijkamp FP. Airway epithelium: more than just a barrier! Trends Pharmacol Sci. 1998 Aug; 19 (8): 334-41. Review.

Gizycki MJ, Adelroth E, Rogers AV, O'Byrne PM, Jeffery PK. Myofibroblast involvement in the allergen-induced late response in mild atopic asthma. Am J Respir Cell Mol Biol. 1997 Jun; 16 (6): 664-73.

Harkema JR, Hotchkiss JA. In vivo effects of endotoxin on nasal epithelial mucosubstances: quantitative histochemistry. Exp Lung Res. 1991 Jul-Aug; 17 (4): 743-61.

Knight DA, Holgate ST. The airway epithelium: structural and functional properties in health and disease. Respirology. 2003 Dec; 8 (4): 432-46. Review.

Spina D. Epithelium smooth muscle regulation and interactions. Am J Respir Crit Care Med. 1998 Nov; 158 (5Pt3): S141-5. Review.

[page 432]

However, it constitutes the interface between the internal milieu and the external environment as well as being a primary target for inhaled respiratory drugs. [...]

[...]

At least eight morphologically distinct epithelial cell types are present in human respiratory epithelium, although based on ultrastructural, functional and biochemical criteria these may be classified into three

[page 433]

categories: basal, ciliated and secretory.1 [...]

Columnar ciliated epithelial cells

Ciliated epithelial cells are the predominant cell type within the airways, accounting for over 50% of all epithelial cells.1 [...] Typically, ciliated epithelial cells possess up to 300 cilia/cell and numerous mitochondria immediately beneath the apical surface, highlighting the primary role of these cells, namely the directional transport of mucus from the lung to the throat.3

Mucous cells (goblet cells)

[...] Production of the correct amount of mucus and the viscoelasticity of mucus are important for efficient mucociliary clearance. [...] These cells are thought to be capable of self-renewal and may also differentiate into ciliated epithelial cells.7

Serous cells

[...] The chemical composition of the granules has not been extensively characterized, although the same cell-type in rat airways contains neutral mucin and an unidentified non-mucoid substance.

Basal cells

Basal cells are ubiquitous in the conducting epithelium, although the number of these cells decreases with airway size.7,9 There is a direct correlation between the thickness of the epithelium and the number of basal cells as well as the percentage of columnar cell attachment to the basement membrane via the basal cell. [...]

Similar to the skin, the basal cell is thought to be the primary stem cell, giving rise to the mucous and ciliated epithelial cells. [...] In smaller airways, where basal cells are sparse or absent, Clara cells perform the primary stem cell role.

In addition to their progenitor and structural roles, basal cells are also thought to secrete a number of bioactive molecules including neutral endopeptidase, 15-lipoxygenase products and cytokines.

Clara cells

In humans, Clara cells are located in large (bronchial) and small (bronchiolar) airways. The cells contain electron-dense granules, thought to produce bronchiolar surfactant and are also characterized by agranular endoplasmic reticulum in the apical cytoplasm and granular endoplasmic reticulum basally. In addition to their secretory role, Clara cells are believed to metabolize xenobiotic compounds by the action of p450 mono-oxygenases and may also produce specific antiproteases such as secretory leukocyte protease inhibitor.13


1 Spina D. Epithelium smooth muscle regulation and interactions. Am. J. Respir. Crit. Care Med. 1998; 158: S141–5.

3 Harkema JR, Mariassy A, St. George J, Hyde DM, Plopper CG. Epithelial cells of the conducting airways: a species comparison. In: Farmer SG, Hay DWP (eds). The Airway Epithelium: Physiology, Pathophysiology and Pharmacology. Marcel-Dekker, New York, 1991; 3–39.

7 Evans MJ, Plopper CG. The role of basal cells in adhesion of columnar epithelium to airway basement membrane. Am. Rev. Respir. Dis. 1988; 138: 481–3.

9 Evans MJ, Cox RA, Shami SG, Plopper CG. Junctional adhesion mechanisms in airway basal cells. Am. J. Respir. Cell. Mol. Biol. 1990; 3: 341–7.

13 De Water R, Willems LN, Van Muijen GN et al. Ultrastructural localization of bronchial antileukoprotease in central and peripheral human airways by a goldlabeling technique using monoclonal antibodies. Am. Rev. Respir. Dis. 1986; 133: 882–90.

Anmerkungen

The source is mentioned twice: once for the statement "Serous cells are also secreting cells and produce neutral mucin and a yet unidentified non-mucoid substance" and once for the statement "In addition to their progenitor and structural roles, basal cells are also thought to secrete a number of bioactive molecules including neutral endopeptidase, 15-lipoxygenase products and cytokines", but not for the rest of the page, which is a shortened and slightly adapted copy of the source, including references to the literature.

Sichter
(Hindemith) Schumann


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