Autotoxicity of Nitric Oxide in Airway Disease

Flak, Tod A.; Goldman, William E.

doi:10.1164/ajrccm/154.4_pt_2.s202

Cited by 68 publications

(54 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…3E and F). Typically, after B. pertussis has bound to ciliated cells, damage to the epithelium is caused by secretion of inducible nitric oxide synthase by secretory cells, which is induced by the bacterial tracheal cytotoxin and endotoxin (10,11).…”

Section: Discussionmentioning

confidence: 99%

Infection of Newborn Piglets with Bordetella pertussis : a New Model for Pertussis

et al. 2005

View full text Add to dashboard Cite

Bordetella pertussis is the causative agent of pertussis or whooping cough. This bacterium is a human pathogen that under experimental conditions also infects selected rodents and primates. Here, we show for the first time that newborn piglets can be infected with B. pertussis when it is delivered intrapulmonarily. Infected piglets displayed fever and respiratory symptoms, such as nasal discharge, nonparoxysmal coughing, and breathing difficulties. Eventually, all infected animals developed severe bronchopneumonia, which in some cases was combined with a fibrinous pleuritits. Immunohistochemical staining revealed the presence of large numbers of B. pertussis cells within airways, adhering to the epithelial lining or phagocytosed by macrophages and neutrophils. Viable bacteria were reisolated from bronchoalveolar lavages and lung lesions for more than 10 days postinfection. The systemic presence of pertussis toxin was shown by hypoglycemia, lymphocytosis, and induction of a clustered pattern of CHO cells by serum and bronchoalveolar lavage samples. Thus, a largeanimal model for pertussis was developed, which should complement existing rodent models for identifying the immune responses relevant to the design of new vaccines. In particular, this model should help researchers analyze the roles of both maternal and mucosal immunity in disease protection against pertussis and should ultimately assist in the design of new vaccines for early life protection.

show abstract

Section: Discussionmentioning

confidence: 99%

Infection of Newborn Piglets with Bordetella pertussis : a New Model for Pertussis

et al. 2005

View full text Add to dashboard Cite

show abstract

“…It is well known that there are many mechanisms of host defense cells that are implicated in these types of pulmonary pathology, when the response of the defense cells is excessive. These include the release of reactive oxygen species by neutrophils and macrophages (15,71,73) and possibly the release of reactive nitrogen species (14,48). Both macrophages and neutrophils release a variety of proteolytic enzymes, including metalloproteinases and elastase, that are capable of degrading the extracellular matrix and effecting structural integrity (9,47).…”

Section: Discussionmentioning

confidence: 99%

Absence of the Macrophage Mannose Receptor in Mice Does Not Increase Susceptibility toPneumocystis cariniiInfection In Vivo

et al. 2003

View full text Add to dashboard Cite

Host defense against the opportunistic pathogen Pneumocystis carinii requires functional interactions of many cell types. Alveolar macrophages are presumed to be a vital host cell in the clearance of P. carinii, and the mechanisms of this interaction have come under scrutiny. The macrophage mannose receptor is believed to play an important role as a receptor involved in the binding and phagocytosis of P. carinii. Although there is in vitro evidence for this interaction, the in vivo role of this receptor in P. carinii clearance in unclear. Using a mouse model in which the mannose receptor has been deleted, we found that the absence of this receptor is not sufficient to allow infection by P. carinii in otherwise immunocompetent mice. Furthermore, when mice were rendered susceptible to P. carinii by CD4؉ depletion, mannose receptor knockout mice (MR-KO) had pathogen loads equal to those of wild-type mice. However, the MR-KO mice exhibited a greater influx of phagocytes into the alveoli during infection. This was accompanied by increased pulmonary pathology in the MR-KO mice, as well as greater accumulation of glycoproteins in the alveoli (glycoproteins, including harmful hydrolytic enzymes, are normally cleared by the mannose receptor). We also found that the surface expression of the mannose receptor is not downregulated during P. carinii infection in wild-type mice. Our findings suggest that while the macrophage mannose receptor may be important in the recognition of P. carinii, in vivo, this mechanism may be redundant, and the absence of this receptor may be compensated for.Pulmonary host defense typically involves cooperation among many cell types, including resident epithelium and macrophages as well as circulating inflammatory cells. However, the importance of each type of cell may differ, depending on the nature of the pathogen presented. Infection with the opportunistic fungus Pneumocystis carinii, which causes often-fatal pneumonia in immunocompromised patients, is an example of a disease process in which many cell types have important but distinct roles. The appearance of antibodies against P. carinii by age 2 in most children, coupled with the low occurrence of the disease in healthy people, led early investigators to conclude that humoral immunity and B cells were of primary importance in host defense against P. carinii (reviewed in reference 68). However, the high incidence of P. carinii infections in AIDS patients (42, 43) and later experimental mouse models highlights the crucial importance of CD4 ϩ lymphocytes in the control of P. carinii infections (5,20).In spite of their importance, CD4 ϩ lymphocytes are probably not involved with the major effector mechanisms against P. carinii (21, 52); instead, this role probably falls to CD8 ϩ lymphocytes, antibodies, and macrophages. Although the importance of CD8 ϩ cells in defense against P. carinii (3, 27) as well as their role in host tissue damage (74) is evident, the mechanisms by which these cells cause these responses are not clear. And although ther...

show abstract

“…It is hypothesized that, in vivo, TCT stimulates IL-1␣ production in nonciliated mucus-secreting cells, which positively controls the expression of inducible nitric oxide synthase, leading to high levels of NO F production. NO F then diffuses to neighboring ciliated cells, which are much more susceptible to its damaging effects (250). TCT also functions synergistically with Bordetella LPS to induce the production of NO F within the airway epithelium (251).…”

Section: Virulence Determinantsmentioning

confidence: 99%

Molecular Pathogenesis, Epidemiology, and Clinical Manifestations of Respiratory Infections Due toBordetella pertussisand OtherBordetellaSubspecies

2005

View full text Add to dashboard Cite

Bordetella respiratory infections are common in people (B. pertussis) and in animals (B. bronchiseptica). During the last two decades, much has been learned about the virulence determinants, pathogenesis, and immunity of Bordetella. Clinically, the full spectrum of disease due to B. pertussis infection is now understood, and infections in adolescents and adults are recognized as the reservoir for cyclic outbreaks of disease. DTaP vaccines, which are less reactogenic than DTP vaccines, are now in general use in many developed countries, and it is expected that the expansion of their use to adolescents and adults will have a significant impact on reducing pertussis and perhaps decrease the circulation of B. pertussis. Future studies should seek to determine the cause of the unique cough which is associated with Bordetella respiratory infections. It is also hoped that data gathered from molecular Bordetella research will lead to a new generation of DTaP vaccines which provide greater efficacy than is provided by today's vaccines

show abstract

Autotoxicity of Nitric Oxide in Airway Disease

Cited by 68 publications

References 38 publications

Infection of Newborn Piglets with Bordetella pertussis : a New Model for Pertussis

Infection of Newborn Piglets with Bordetella pertussis : a New Model for Pertussis

Absence of the Macrophage Mannose Receptor in Mice Does Not Increase Susceptibility toPneumocystis cariniiInfection In Vivo

Molecular Pathogenesis, Epidemiology, and Clinical Manifestations of Respiratory Infections Due toBordetella pertussisand OtherBordetellaSubspecies

Contact Info

Product

Resources

About