Biomedical subjects

Marsha Wills-Karp

Publications and source records attributed to Marsha Wills-Karp.

4 recordsLinked to original sources

PubMed2003

Interleukin-13 in asthma.

Some time ago, the Th2 cytokine, interleukin (IL)-13, was identified as a critical regulator of the allergic response. Initial studies in animal models of disease provided compelling evidence that IL-13, independent from other Th2 cytokines, was necessary and sufficient to induce all features of allergic asthma. This contention was supported in human disease when strong associations between IL-13 levels and genetic polymorphisms in the IL-13 gene and disease correlates were found. With the preponderance of evidence continuing to support the importance of IL-13 in allergic disorders, attention is now turned towards understanding the mechanisms by which this cytokine may mediate the pathophysiologic features of allergic disease. The emerging paradigm is that IL-13 induces features of the allergic response via its actions on epithelial and smooth muscle cells not through traditional effector pathways involving eosinophils and IgE-mediated events. In light of recent developments, this review will explore our current understanding of the role of IL-13 in the pathogenesis of allergy and asthma with a particular focus on new insights into the mechanisms by which IL-13 induces the features of asthma.

Animals↗

PubMed2002

A role for immune complexes in enhanced respiratory syncytial virus disease.

Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and viral pneumonia in infants and young children. Administration of a formalin inactivated vaccine against RSV to children in the 1960s resulted in increased morbidity and mortality in vaccine recipients who subsequently contracted RSV. This incident precluded development of subunit RSV vaccines for infants for over 30 years, because the mechanism of illness was never clarified. An RSV vaccine for infants is still not available. Here, we demonstrate that enhanced RSV disease is mediated by immune complexes and abrogated in complement component C3 and B cell-deficient mice but not in controls. Further, we show correlation with the enhanced disease observed in children by providing evidence of complement activation in postmortem lung sections from children with enhanced RSV disease.

Animals↗

PubMed2002

Amb a 1-linked CpG oligodeoxynucleotides reverse established airway hyperresponsiveness in a murine model of asthma.

BACKGROUND: Recently, it has been demonstrated that immunostimulatory DNA sequences (ISS) containing CpG motifs prevent the development of allergic airway responses in murine models of disease. However, few studies have addressed the issue of whether these agents will reverse established Tm(H)2-driven allergic airway responses. OBJECTIVE: The aim of this study was to determine whether intradermal delivery of an immunogenic protein of ragweed pollen linked to an immunostimulatory DNA sequence could reverse an established allergic response in the mouse lung. METHODS: Mice sensitized and challenged with ragweed pollen extract were treated intradermally twice at 1-week intervals with an ISS chemically linked to Amb a 1 (Amb a 1-ISS). One week after the Amb a 1-ISS treatment, mice were rechallenged intratracheally with ragweed extract, and airway responses were assessed. RESULTS: Amb a 1-ISS treatment of ragweed-sensitized and ragweed-challenged mice significantly reversed allergen-induced airway hyperresponsiveness and suppressed the total number of eosinophils in bronchoalveolar lavage fluid. The inhibitory effect of Amb a 1-ISS was associated with a marked increase in IFN-gamma levels by Amb a 1-stimulated splenocytes and a shift in the antibody profile from a T(H)2-directed IgG1 response to a T(H)1-directed IgG2a response. Interestingly, the inhibitory effect of Amb a 1-ISS on allergen-driven airway hyperresponsiveness was independent of suppression of T(H)2 cytokine production. CONCLUSION: These results demonstrate that intradermal delivery of allergen-specific DNA conjugates can reverse established allergic responses in the murine lung, supporting their potential use in the treatment of human asthma.

Adjuvants, Immunologic↗

PubMed2002

Complement factor 3 mediates particulate matter-induced airway hyperresponsiveness.

Epidemiologic studies have suggested that exposure to airborne particulate matter (PM) can exacerbate allergic airway responses; however, the mechanism(s) are not well understood. We and others have recently shown that development of airway hyperresponsiveness (AHR) may be a complement-mediated process. In the present study, we examined the role of complement factor 3 (C3) in the development of PM-induced AHR and airway inflammation by comparing responses between C3-deficient (C3(-/-)) and wild-type mice. Mice were exposed to 0.5 mg of ambient particulate collected in urban Baltimore. Forty-eight hours later, airway responsiveness to intravenous acetylcholine was assessed and bronchoalveolar lavage was conducted. PM exposure of wild-type mice resulted in significant increases in AHR, whereas it did not significantly increase airway reactivity in C3(-/-) mice. Interestingly, PM induced similar inflammatory responses in both wild-type and C3(-/-) mice. Immunohistochemical staining demonstrated marked C3 deposition in the airway epithelium and connective tissue of wild-type mice after PM exposure. These results suggest that exposure to PM may induce AHR through activation of complement factor 3 in the airways.

Air Pollution↗