Alveolar epithelial cells: differentiation and lung injury

Abstract:   Re-epithelialization of alveolar epithelial cells is one of the important repair processes in many types of lung injury. The major functions of alveolar type II cells are synthesis and secretion of surfactant, hyperplasia in reaction to alveolar epithelial injury, and serving as progenitor cells for alveolar type I cells. The authors have examined the effects of several soluble factors on cultured alveolar type II cells in vitro , and also examined the histopathology and gene expression of surfactant proteins in the rat lungs with LPS, bleomycin and/or treated with keratinocyte growth factor. The authors next examined the effects of bone marrow stromal cells (BMSC) implanted transvenously into bleomycin-induced lungs. The authors found that keratinocyte growth factor (KGF) is a strong growth factor for alveolar type II cells, and that KGF instillation prevents bleomycin-induced lung injury. Furthermore, the authors showed the possibility of differentiation of implanted BMSC into alveolar epithelial cells. KGF and BMSC may play an important role in maintaining the alveolar epithelium and repairing the damaged epithelium after injury, and may well provide potential therapeutic alternatives.     

Genotoxic Properties of (E)-5-(2-Bromovinyl)-2'-deoxyuridine (BVDU)

(E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) is a 5-substituted2'-deoxyuridine antiviral compound that inhibits thymidylatesynthetase. The selectivity of BVDU for virus-infected cellshas been attributed to phosphorylation of BVDU by a virus-inducedthymidine kinase. Since the closely related compounds 5-bromo-2'-deoxyuridineand 5-iodo-2'-deoxyuridine are in vitro and in vivo mutagens,BVDU was tested for genotoxic activity in bacterial and mammaliancell mutation assays as well as in assays measuring DNA damage/repairand clastogenic activity. Mutation assays with BVDU at concentrationsranging from 10 to 5000 µg/plate using Salmonella typhimuriumstrains TA1535, TA1537, TA1538, TA98, and TA100 were negative,both with and without S9 activation. BVDU was also negativein the in vitro rat hepatocyte unscheduled DNA synthesis assayat concentrations of 750 and 1000 µg/ml. In contrast,BVDU was positive in the L5178Y TK^± mouse lymphoma mutationassay without S9 activation at five concentrations ranging from500 to 2000 µg/ml. A Chinese hamster ovary cell (CHO)/hypoxanthineguanine phosphoribosyl transferase gene mutation assay conductedwithout S9 over similar concentrations was negative. However,micronucleus induction by BVDU was detected with out S9 activationat concentrations between 500 and 1750 µg/ml using bothCHO and L5178Y cells. These results indicate that BVDU is apotential human clastogen.