Respir Cell Mol Biol Research Articles

Expression of Surfactant-Associated Protein A in the Fetal Rat Gastrointestinal Tract † 562

Gastrointestinal epithelium produces surface-active material closely related to that produced by pulmonary alveolar type II epithelial cells. This material includes surfactant-associated protein A (SP-A) which may play a role in gut defense mechanisms. Rubio et al. (J Biol Chem 270:12162, 1995) first demonstrated SP-A in the large and small intestines but not in the stomach of the adult rat. To ascertain the ontogeny and localization of gastrointestinal SP-A we investigated the expression of mRNA in fetal rat gut using RT-PCR with nested primers. Amplification of the cDNA yielded appropriately sized SP-A bands (372 base pairs) in the 17-day fetal rat stomach and intestine; 18-day fetal rat stomach and intestine; 20- and 21-day fetal rat stomach, small intestine and large intestine. These findings were correlated with SP-A expression in the adult rat lung as a positive control and the lack of SP-A expression in the adult rat kidney as a negative control. This is the first documentation of SP-A expression by the fetal rat gastrointestinal tract. Expression of pulmonary SP-A by the fetal rat was reported at gestational day 15.5 by in situ hybridization(Meneghetti, et al. J Histochem Cytochem 44:1173,1996) and at gestational day 13 by RT-PCR (Wang, et al. Am J Respir Cell Mol Biol 10:222, 1994). Our on-going studies are aimed at quantitative analysis of the temporal and spatial profile of SP-A expression in the rat G.I. tract and its possible role in gut defenses.

Current research and future needs in allergic rhinitis and asthma

Although effective therapies are available to treat asthma and allergic rhinitis, research is now focused on defining the cause of these disorders, including an in-depth analysis of the role of the inflammatory process. An enhanced understanding of the mechanism of the asthmatic inflammatory response should aid in the discovery of more-targeted therapies and preventative

Investigational agents for the treatment of asthma

The approach to the treatment of asthma has changed considerably over the years. Initial treatments for asthma were designed to relieve symptoms and included epinephrine, atropine-like drugs, and inhalers such as albuterol. Subsequently, as the inflammatory processes involved in asthma were better understood, agents were developed to decrease these processes. These agents include corticosteroids, theophylline, and cromones. The precise mechanism of action of these drugs has remained unclear. Recently, however, important studies have revealed information regarding causes of asthma including the interrelationships among specific immune cells, cytokines, and other immune mediators. This knowledge has led to tailored treatment approaches and improved application of nonspecific anti-inflammatory drugs in the treatment of asthma. In addition, more specifically targeted agents have been and continue to be developed. Combinations of nonspecific and specific agents may further improve the treatment of asthma. NONSPECIFIC CONTROL OF CELLULAR INFLAMMATION Newer agents that can be categorized as nonspecific controllers of cellular inflammation include some of the newly developed inhaled corticosteroids and noncorticosteroid anti-inflammatory agents. Inhaled corticosteroids

The cellular and mediator basis of asthma in relation to natural history

The cellular and mediator basis of asthma in relation to natural history

The Effects of Sialoglycoconjugates on Adenovirus-Mediated Gene Transfer to Epithelial Cells In Vitro and in Human Airway Xenografts

Recombinant adenoviruses are currently being developed as gene transfer vectors for the treatment of various lung diseases. 1 Curiel DT Pilewski JM Albelda SM Gene therapy approaches for inherited and acquired lung diseases.. Am J Respir Cell Mol Biol. 1996; 14: 1-18 Crossref PubMed Scopus (96) Google Scholar Studies have demonstrated that recombinant adenoviruses mediate high-efficiency gene transfer to cultured airway epithelial cells, but markedly lower efficiency to primate and human conducting airway epithelium. 1 Curiel DT Pilewski JM Albelda SM Gene therapy approaches for inherited and acquired lung diseases.. Am J Respir Cell Mol Biol. 1996; 14: 1-18 Crossref PubMed Scopus (96) Google Scholar , 2 Zabner J Ramsey BW Meeker DP et al. Repeat administration of an adenovirus vector encoding cystic fibrosis transmembrane conductance regulator to the nasal epithelium of patients with cystic fibrosis.. J Clin Invest. 1996; 97: 1504-1511 Crossref PubMed Scopus (237) Google Scholar This suggests the existence of barriers to adenovirus-mediated gene transfer to differentiated epithelium. Several potential barriers include cilia, tight junctions and polarized receptor expression, and apical membrane glycoconjugates such as mucins.

Transient Gene Transfer and Expression in the Lung

To many investigators, the concept of gene therapy involves the permanent transfer of a normal gene to the genome of an individual to replace a nonfunctioning (mutated) gene with reversal or prevention of the onset of the disease process. Just as valid would be the temporary introduction of a normal gene to tissues without genomic integration, resulting in transient gene expression and production of the functional gene product to modify tissue responses or provide temporary protection from pathogenic mechanisms. Such a concept may be applicable to treatment of pulmonary disorders by delivering a variety of cytokines. While these factors can be administered in the recombinant state, the difficulty of targeting the lung tissue and the short half-life of these cytokine mediators in circulation limits their use and makes the transient gene transfer approach a preferable alternate. This is particularly so for the consideration of the use of cytokines in immunotherapy of cancer. The topic of gene therapy in the lung and the vectors needed has recently been comprehensively reviewed by Curiel et al. 1 Curiel DT Pilewski JM Albelda SM Gene therapy approaches for inherited and acquired lung diseases.. Am J Respir Cell Mol Biol. 1996; 14: 1-18 Crossref PubMed Scopus (97) Google Scholar

Basophil and eosinophil differentiation in allergic reactions

Basophil and eosinophil participation in allergic reactions constitutes a hallmark of this type of inflammatory state. Mechanisms underlying the accumulation of these cells in tissues where allergen is present include the effect of cytokines and other inflammatory mediators on the egress from blood and migration of these cells into the tissue. Much progress has been made recently in the understanding of in vitro chemotactic and adherence mechanisms putatively involved in the accumulation of the mature basophil and eosinophil in IgE-dependent reactions in vivo? A concept we have developed in our studies over the past decade is that the bone marrow, through the release of progenitors into the peripheral blood, contributes a pool of differentiating cells, which accumulate in response to signals from allergic inflamed tissues. 2s In this review we summarize the basis for this concept, citing both basic and applied studies and expanding on the evidence supporting the progenitor hypothesis for accumulation of basophils and eosinophils by using recently acquired information in an animal model and in human beings.

Basophils and eosinophils in allergic rhinitis

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Asthma ‘Of Mice and Men’–How do animal models help us understand human asthma?

Asthma ‘Of Mice and Men’–How do animal models help us understand human asthma?

In Situ Regulation of Pulmonary Macrophage TNF-α mRNA Expression by IL2

The antitumor activity of IL2, used either alone or in combination with the adoptive transfer of activated lymphocytes, is well known. 1 Rosenberg SA Lotze MA Muul LM et al. A progress report on the treatment of 157 patients with advanced cancer using lymphokine activated killer cells and interleukin 2 or high dose interleukin 2 alone. N Engl J Med. 1887; 316: 887-889 Google Scholar , 2 Kradin RL Lazarus DS Dubinett SM et al. Tumor-infiltrating lymphocytes and interleukin-2 in the treatment of patients with advanced cancer. Lancet. 1889; 1: 577-580 Google Scholar , 3 Dubinett SM Kurnick JT Kradin RL Adoptive immunotherapy of murine pulmonary metastases with interleukin 2 and interferon-gamma. Am J Respir Cell Mol Biol. 1989; 1: 361-369 Crossref PubMed Scopus (16) Google Scholar However, the use of IL2, a 15 kd glycoprotein produced by activated T lymphocytes, as an antitumor agent has been limited by severe dose-dependent toxicities, including a diffuse vascular leak syndrome and shock. 4 Ognibene FP Rosenberg SA Lotze M et al. Interleukin-2 administration causes reversible hemodynamic changes and left ventricular dysfunction similar to those seen in septic shock. Chest. 1988; 94: 750-754 Abstract Full Text Full Text PDF PubMed Scopus (153) Google Scholar , 5 Lee RE Lotze MT Skibber JM et al. Cardiorespiratory effects of immunotherapy with interleukin-2. J Clin Oncol. 1989; 7: 7-20 Crossref PubMed Scopus (227) Google Scholar Indeed, the pathophysiologic consequences of high-dose IL2 are remarkably similar to those seen in septic shock. 4 Ognibene FP Rosenberg SA Lotze M et al. Interleukin-2 administration causes reversible hemodynamic changes and left ventricular dysfunction similar to those seen in septic shock. Chest. 1988; 94: 750-754 Abstract Full Text Full Text PDF PubMed Scopus (153) Google Scholar Several recent investigations have identified tumor necrosis factor-alpha (TNF-α) as an important mediator of toxicity in endotoxemia and Gram-negative sepsis. 6 Tracey KJ Fong Y Hesse DG et al. Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia. Nature. 1987; 330: 662-664 Crossref PubMed Scopus (2003) Google Scholar , 7 Beutler B Milsark IW Cerami AC Passive immunization against cachetin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science. 1985; 229: 869-871 Crossref PubMed Scopus (1853) Google Scholar , 8 Schirmer WJ Schirmer JM Fry DE Recombinant human tumor necrosis factor produces hemodynamic changes characteristic of sepsis and endotoxemia. Arch Surg. 1989; 124: 445-448 Crossref PubMed Scopus (99) Google Scholar The clinical similarities between IL2 toxicity and sepsis suggest that TNF-α may be a mediator of some of the toxic effects associated with IL2.