The primary target of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is epithelial cells in the respiratory and intestinal tract. The cellular receptor for SARS-CoV, angiotensin-converting enzyme 2 (ACE2), has been shown to be localized on the apical plasma membrane of polarized respiratory epithelial cells and to mediate infection from the apical side of these cells. Here, these results were confirmed and extended by including a colon carcinoma cell line (Caco-2), a lung carcinoma cell line (Calu-3) and Vero E6 cells in our analysis. All three cell types expressed human ACE2 on the apical membrane domain and were infected via this route, as determined with vesicular stomatitis virus pseudotypes containing the S protein of SARS-CoV. In a histological analysis of the respiratory tract, ACE2 was detected in the trachea, main bronchus and alveoli, and occasionally also in the small bronchi. These data will help us to understand the pathogenesis of SARS-CoV infection.Epithelia are a primary barrier to infection by microorganisms entering their host via body cavities such as the respiratory or intestinal tract (reviewed by Compans & Herrler, 2005). Epithelial cells are organized in a polarized fashion that involves the separation of the plasma membrane into an apical and a basolateral domain. The polarity of these cells affects both the early and late stages of infection, i.e. viruses may enter into and exit from a cell either via the apical membrane facing the external environment or via the basolateral membrane directed to the internal milieu of the organism. An important determinant of the virus infection is the presence of suitable receptors on the cell surface that allow attachment to and penetration through the plasma membrane. For viruses entering their host via the respiratory or gastrointestinal route, infection is understood most easily when the virus receptor is expressed on the apical surface.The primary target of the coronavirus associated with severe acute respiratory syndrome (SARS-CoV) is the respiratory tract. In addition to respiratory complications, some patients show intestinal symptoms, indicating that not only the respiratory but also the intestinal epithelium is susceptible to infection. It has been shown recently that the receptor for SARS-CoV, angiotensin-converting enzyme 2 (ACE2; Li et al., 2003;Wang et al., 2004), is localized on and mediates infection through the apical plasma membrane of respiratory epithelial cells (Jia et al., 2005;Sims et al., 2005; Tseng et al., 2005). On the other hand, ACE2 has been reported to be absent from enterocytes of the colon (Hamming et al., 2004), despite active replication of SARS-CoV in this portion of the intestine (Leung et al., 2003).To determine whether epithelial cells of different origin differ in the expression of ACE2, we included in our analysis three cell lines that form a highly polarized epithelial monolayer when grown on microporous filters: (i) Calu-3 (human lung carcinoma cells), (ii) Caco-2 (human colon carcinoma ce...

Bronchus-associated lymphoid tissue (BALT) was first described in the lungs of rabbits and differs greatly between species. It is part of the integrated mucosal immune system. This review clarifies its morphological definition and focuses on the situation in humans. The frequency of BALT at different ages, after chronic stimulation and in different diseases is described. In healthy humans, BALT can only be found in the lungs of children and adolescents. The role of BALT in lung transplantation and in the development of low-grade malignant lymphomas in the airways is also discussed. Furthermore, questions concerning the inducibility of BALT as an entry site for vaccines, and the regulation of its activity for future therapeutic interventions in pulmonary immune reactions are addressed.

Allergic asthma is thought to be the result of an inappropriate specific immune response against common environmental antigens. However, studies of animal asthma models have also linked the innate immune system, in particular complement factors C3a and C5, to murine airway hyperresponsiveness. Because the possible role of these anaphylatoxins in patients with asthma is not understood, we tested the hypothesis that C3a and C5a will increase in the bronchoalveolar lavage (BAL) fluid of patients with asthma after segmental allergen provocation. In a group of 15 subjects with mild asthma we found a significant upregulation of C3a and C5a 24 h after allergen challenge compared with baseline values (p < 0.01). In a control group of healthy volunteers the concentrations remained basically unchanged. Furthermore, we found a strong correlation between both anaphylatoxins and the number of eosinophils (p < 0.01) and, to a lesser degree, with the number of neutrophils (p < 0.05) in BAL fluid. These data suggest a contribution of anaphylatoxins C3a and C5a to the pathogenesis in asthma. However, the pathogenic role of these substances in relation to asthma remains to be elucidated, for example, by using anaphylatoxin receptor blockers as a possible new therapeutic principle.

Alveolar surfactant is well known for its ability to reduce minimal surface tension at the alveolar air-liquid interface to values below 5 mN/m. In addition, it has been suggested that an analogous conductive airway surfactant is also present in the airways. To elucidate the composition, possible origin, and surface activity of conductive airway phospholipids (PL), we compared in adult porcine lungs the PL classes and phosphatidylcholine (PC) molecular species of nonpurified tracheal aspirate samples with those of bronchoalveolar lavage fluid (BAL), tracheobronchial epithelium, and lung parenchyma. We also analyzed PL and PC composition, protein content, and surface activity of surfactant isolated from tracheal aspirates (SurfTrachAsp), BAL (SurfBAL), and the 27,000 x g pellet of BAL (SurfP27000) by density-gradient centrifugation. Although PL composition revealed contributions of the airways to tracheal aspirates, the composition of PC molecular species of tracheal aspirates was similar to that of BAL and lung parenchyma, but differed considerably from that of airway epithelium. SurfTrachAsp had the same PL and PC composition as SurfBAL and SurfP27000, indicating that this fraction of tracheal aspirates may have originated from the alveoli. Nevertheless, minimal and maximal surface tensions were higher in SurfTrachAsp than in SurfBAL and SurfP27000. Analysis of surfactant proteins A, B, and C (SP-A, SP-B, and SP-C) revealed that SP-A was decreased and SP-B and SP-C were absent, whereas total protein was increased in SurfTrachAsp. We conclude that as compared with alveolar surfactant, PL of SurfTrachAsp show the same composition, but that surface-tension function is impaired and the concentration of surfactant proteins is decreased in SurfTrachAsp.