Chest
Volume 96, Issue 1, July 1989, Pages 165-173
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Influence of the Extracellular Matrix on Type 2 Cell Differentiation

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Growth and division of type II pulmonary epithelial cells are important components of the pathway by which the alveolar surface is repaired following several forms of lung injury. These processes, which result in reepithelialization of the denuded alveolar basement membrane, involve loss of type II cell differentiation and transition to a type I epithelium. As in other cells, the extracellular matrix appears to be an important determinant of type II cell differentiation. This effect on the type II cell is exerted by both simple and complex matrices and may be modulated by active synthesis and remodeling of the matrix components by the pneumocytes themselves. In general, laminin or laminin-rich complex surfaces favor cellular differentiation; fibronectin or fibronectin-rich complex matrices accelerate loss of differentiated form and function. In both cases, matrix-initiated changes in the type II cell involve regulation of cell shape and morphology, hormone responsiveness, secretory activity, phospholipid synthesis, protein turnover, and gene expression. These influences of the extracellular matrix, along with the effects of locally acting soluble factors, likely direct the cellular transitions required for restoration of a physiologically competent alveolar surface during the repair of lung injury.

Section snippets

The Role of the Type II Cell in Lung Function and Repair

Over the past 15 years, investigations of the metabolism and cell biology of the lung have joined those of more classic aspects of pulmonary physiology as significant components of the literature on pulmonary biology and medicine. This broadening of emphasis in pulmonary research reflects the recognition that both the metabolic and gas exchange activities of the lung determine the overall physiologic functions of the tissue. Ultimately, these functions must be accounted for at the cellular and

Characteristics of the Differentiated Type II Cell

Subsequent to definition of the general cellular changes which follow acute injury, there has been a considerable growth of interest in the role of the type II cell in this process. Because this response involves cell growth and division, along with a transition of the type II cell to a type I phenotype, progress in this area has required that specific, quantifiable indices of the extent of type II cell differentiation be identified and validated. These characteristics have served as markers to

Influence of the Extracellular Matrix on Epithelial Differentiation and Function

The extracellular matrix is known to influence the differentiation and metabolism of a variety of cell types, based on detailed analysis of their interactions with both simple and complex culture surfaces of defined composition.26, 27, 28 These include cells of the nervous system,29 smooth muscle cells,30 hepatocytes,31,32 fibroblasts,33,34 endothelial cells,35 and epithelial cells.27,36 The classic studies which established precedent for the biologic significance of the extracellular matrix in

Role of Extracellular Matrix in Regulation of Type II Cell Differentiation

Type II cells cultured on plastic surfaces are characterized by progressive flattening and rapid loss of differentiation. These transitions in morphology and function are, in a general way, analogous to those cited above in the mammary epithelial cell model. On the other hand, they also bear striking resemblance to the type II cell transitions required for repair of the alveolar surface following acute lung injury. Evaluation of the cells based on a number of the criteria outlined in Table 1,

Effects of Fibronectin on the Type II Cell

Fibronectin-coated surfaces promote attachment, spreading, and loss of differentiation by type II cells in primary culture.19,49 Attachment is mediated by a specific cell attachment domain of the fibronectin molecule; this activity is blocked by monoclonal antibodies against this, but not against other domains of the polypeptide.49 Thymidine incorporation by type II cells is also stimulated by a fibronectin-coated culture surface, and this effect is blocked by pretreatment of the matrix with

Effects of Laminin and Of Laminin-Rich Complex Matrix Derived from EHS Sarcoma

Laminin is a multifunctional glycoprotein present in the basement membranes of most cells,26 including both fetal and adult type II pneumocytes.57,65,67 Primary cultures of type II cells plated on dishes coated with purified laminin do not adhere as rapidly as do cells exposed to fibronectin.49 Similarly, culture-associated changes in cell morphology are less rapid on laminin surfaces than on fibronectin.68 These transient but reproducible effects of the purified glycoprotein complement the

Effects of Complex Extracellular Matrices

One of the most interesting in vitro models for type II cell culture was described by Lwebuga-Mukasa et al,65 where both the basement membrane and stromal surfaces of an acellular human amnionic membrane were used as culture substrata. Both laminin and type IV collagen are localized only on the basement membrane surface of the amnion, along with some type V collagen. Type II cells plated on the basement membrane side of the amnion retain cuboidal morphology, exhibit typical phospholipid

Synthesis, Deposition, and Turnover of the Extracellular Matrix by Type II Cells

Early observations defined the secretion of several matrix components including fibronectin, type IV collagen and thrombospondin by adult type II cells cultured on plastic surfaces.44 More recent work19,45,46 confirmed synthesis and secretion of fibronectin. This observation is consistent with the high fibronectin content of the alveolar basement membrane. Pro-α1(IV) and pro-α2(IV) collagens are also produced, and approximately half of the newly synthesized type IV collagen is associated with

Conclusions

Remodeling and repair of the alveolar surface following lung injury requires a dynamic and rapid cellular response for the restoration of physiologic pulmonary function. The pathway of this repair involves growth and division of type II pulmonary epithelial cells. These processes, which lead to reepithelialization of the denuded alveolar basement membrane, are thought to involve transition of a portion of the differentiated type II cell population to type I epithelium. Factors in the lung

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    Supported by Grant HL-31560 from the National Heart, Lung and Blood Institute of the National Institutes of Health. SRR is an Established Investigator of the American Heart Association.

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