Basic and Clinical ImmunologyEffect of GM-CSF on immune, inflammatory, and clinical responses to ragweed in a novel mouse model of mucosal sensitization☆,☆☆
Section snippets
Animals
Female BALB/c mice (6-8 weeks old) were purchased from Charles River Laboratories (Montreal, Quebec, Canada). The mice were housed in a specific-pathogen-free environment under a 12-hour light-dark cycle. All experiments described here were approved by the Animal Research Ethics Board of McMaster University.
I. Exposure protocol with Ad/GM-CSF
A replication-deficient human type 5 adenoviral construct carrying mouse GM-CSF cDNA in the E1 region of the viral genome (Ad/GM-CSF)1 was delivered intranasally to isoflurane-anesthetized
Clinical assessment
Mice receiving RW alone experienced clinical symptoms that consisted of mild sneezing and face rubbing. Clinical manifestations were observed when the mice had recovered from anesthesia. Symptoms began consistently as early as the third RW administration in all groups. In contrast to mice that received RW alone, mice that received RW in conjunction with Ad/GM-CSF (GM/RW) displayed symptoms that increased in severity with subsequent RW administrations. These animals typically showed, toward the
Discussion
Ragweed is an aeroallergen of considerable clinical relevance, particularly in North America. Despite its importance, there is a limited amount of data available with respect to airway immune-inflammatory responses to ragweed in murine systems. Although a number of groups have established models of ragweed-induced allergic conjunctivitis6, 7, 8, 9, 10, 11, 12 and eosinophilic peritonitis,13, 14, 15 data on airway inflammatory responses to ragweed, as compared with OVA, are surprisingly scarce.
Acknowledgements
We thank Joanna deJong, Stacey A. Ritz, Clinton Robbins, Theresa Shea, Martin R. Stämpfli, and Ryan E. Wiley for both their assistance with experiments and their critical appraisal of the manuscript. We further acknowledge the generous administrative assistance of Mary Kiriakopoulos.
References (39)
- et al.
A new murine model of allergic conjunctivitis and effectiveness of nedocromil sodium
J Allergy Clin Immunol
(1996) - et al.
A novel model of allergic conjunctivitis
Clin Immunol Immunopathol
(1998) - et al.
Blocking ICAM-1 (CD54) and LFA-1 (CD11a) inhibits experimental allergic conjunctivitis
Clin Immunol
(1999) - et al.
The role of IL-12 in the induction of late-phase cellular infiltration in a murine model of allergic conjunctivitis
J Allergy Clin Immunol
(2000) - et al.
Ligation of IgE receptors causes an anaphylactic response and neutrophil infiltration but does not induce eosinophilic inflammation in mice
J Allergy Clin Immunol
(2000) - et al.
On the generation of allergic airway diseases: from GM-CSF to Kyoto
Trends Immunol
(2002) - et al.
Comparison of the functional properties of murine dendritic cells generated in vivo with flt3 ligand, gm-csf and flt3 ligand plus gm-csf
Cytokine
(2002) - et al.
Effect of ozone and nitrogen dioxide on the release of proinflammatory mediators from bronchial epithelial cells of nonatopic nonasthmatic subjects and atopic asthmatic patients in vitro
J Allergy Clin Immunol
(2001) - et al.
Transfer of granulocyte-macrophage colony-stimulating factor gene to rat lung induces eosinophilia, monocytosis, and fibrotic reactions
J Clin Invest
(1996) - et al.
GM-CSF transgene expression in the airway allows aerosolized ovalbumin to induce allergic sensitization in mice
J Clin Invest
(1998)
Immunomodulatory effects of IL-12 on allergic lung inflammation depend on timing of doses
J Immunol
Generation of experimental allergic airways inflammation in the absence of draining lymph nodes
J Clin Invest
Granulocyte macrophage colony-stimulating factor-driv-en respiratory mucosa sensitization induces Th2 differentiation and function independently of interleukin-4
Am J Respir Cell Mol Biol
Soluble P-selectin glycoprotein ligand 1 inhibits ocular inflammation in a murine model of allergy
Invest Ophthalmol Vis Sci
Systemic or mucosa administration of immunostimulatory DNA inhibits early and late phases of murine allergic conjunctivitis
Eur J Immunol
Prevention of acute allergic conjunctivitis with immunostimulatory DNA sequences
Invest Ophthalmol Vis Sci
IL-5 production by NK cells contributes to eosinophil infiltration in a mouse model of allergic inflammation
J Immunol
Multiple, targeted deficiencies in selectins reveal a predominant role for P-selectin in leukocyte recruitment
Proc Natl Acad Sci U S A
Inhibition of specific IgE responses in mice by pre-exposure to inhaled antigen
Immunology
Cited by (48)
Cellular and molecular mechanisms of allergic asthma
2022, Molecular Aspects of MedicineGM-CSF treatment prevents respiratory syncytial virus-induced pulmonary exacerbation responses in postallergic mice by stimulating alveolar macrophage maturation
2016, Journal of Allergy and Clinical ImmunologyCitation Excerpt :In addition, during the effector phase of the allergic airway response, GM-CSF has been shown to exert a proinflammatory role.29-31 Indeed, administration of exogenous GM-CSF to the lungs of OVA-sensitized and OVA-challenged mice increased airway eosinophilia,29,30 whereas prophylactic administration of neutralizing anti–GM-CSF antibodies decreased AAI on OVA inhalation.31,33 Finally, after clearance of inflammation, the present study identifies GM-CSF as a homeostatic regulator controlling the maturation and inflammatory status of rAMs.
A single injection of a sustained-release prostacyclin analog (ONO-1301MS) suppresses airway inflammation and remodeling in a chronic house dust mite-induced asthma model
2013, European Journal of PharmacologyCitation Excerpt :Although ovalbumin-induced airway inflammation shares many features observed in asthmatic individuals, it is not a naturally existing allergen in humans; moreover, chronic exposure without systemic sensitization leads to tolerance (Swirski et al., 2002; Koya et al., 2006; Swirski et al., 2006). Therefore, the use of chronic animal models related to common environmental allergen, such as house dust mite (HDM) (Johnson et al., 2004) and ragweed (Cates et al., 2003), may lead to the elucidation of the mechanisms underlying airway inflammation and remodeling and provide better test systems for the evaluation of novel therapeutic approaches. ONO-1301 is a synthetic prostacyclin agonist that lacks the typical prostanoid structure of a 5-membered ring and allylic alcohol, which renders its metabolization more difficult.
Development of a Murine Model of Airway Inflammation and Remodeling in Experimental Asthma
2009, Archivos de BronconeumologiaAccelerated differentiation of bone marrow-derived dendritic cells in atopic prone mice
2008, International Immunopharmacology
- ☆
Supported by the Canadian Institutes of Health Research. Elizabeth C. Cates is supported by an Ontario Graduate Scholarship.
- ☆☆
Reprint requests: Manel Jordana, MD, PhD, HSC-4H21, Department of Pathology and Molecular Medicine, McMaster University, 1200 Main St W, Hamilton, Ontario, L8S 3Z5, Canada.