Limits...
Ovalbumin sensitization changes the inflammatory response to subsequent parainfluenza infection. Eosinophils mediate airway hyperresponsiveness, m(2) muscarinic receptor dysfunction, and antiviral effects.

Adamko DJ, Yost BL, Gleich GJ, Fryer AD, Jacoby DB - J. Exp. Med. (1999)

Bottom Line: Asthma exacerbations, many of which are virus induced, are associated with airway eosinophilia.An additional and unexpected finding was that sensitization to ovalbumin caused a marked (80%) reduction in the viral content of the lungs.This was reversed by the antibody to IL-5, implicating a role for eosinophils in viral immunity.

View Article: PubMed Central - PubMed

Affiliation: Department of Environmental Health Sciences, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA.

ABSTRACT
Asthma exacerbations, many of which are virus induced, are associated with airway eosinophilia. This may reflect altered inflammatory response to viruses in atopic individuals. Inhibitory M(2) muscarinic receptors (M(2)Rs) on the airway parasympathetic nerves limit acetylcholine release. Both viral infection and inhalational antigen challenge cause M(2)R dysfunction, leading to airway hyperresponsiveness. In antigen-challenged, but not virus-infected guinea pigs, M(2)R dysfunction is due to blockade of the receptors by the endogenous antagonist eosinophil major basic protein (MBP). We hypothesized that sensitization to a nonviral antigen before viral infection alters the inflammatory response to viral infection, so that M(2)R dysfunction and hyperreactivity are eosinophil mediated. Guinea pigs were sensitized to ovalbumin intraperitoneally, and 3 wk later were infected with parainfluenza. In sensitized, but not in nonsensitized animals, virus-induced hyperresponsiveness and M(2)R dysfunction were blocked by depletion of eosinophils with antibody to interleukin (IL)-5 or treatment with antibody to MBP. An additional and unexpected finding was that sensitization to ovalbumin caused a marked (80%) reduction in the viral content of the lungs. This was reversed by the antibody to IL-5, implicating a role for eosinophils in viral immunity.

Show MeSH

Related in: MedlinePlus

Airway leukocyte populations were measured in bronchoalveolar lavage after pretreatment with AbIL5 and AbMBP. In nonsensitized virus-infected animals (black bars, n = 10), pretreatment with AbIL5 (gray bars, n = 5) did not change any of the leukocyte numbers (A). In contrast, pretreatment of sensitized virus-infected animals with AbIL5 (gray bars, n = 8) significantly decreased the number of eosinophils compared with sensitized virus-infected alone (black bars; n = 16, P < 0.0001) (B). Pretreatment of sensitized virus-infected animals with AbMBP (dark gray bars, n = 7) caused a slight but statistically significantly decrease in eosinophil numbers compared with sensitized virus-infected animals alone (black bars; n = 16, P = 0.04). In both AbIL5- and AbMBP-pretreated animals, neutrophil cell numbers were unaltered. Total leukocyte numbers were significantly decreased in sensitized virus-infected animals treated with AbIL5 (light gray bar) compared with sensitized virus-infected animals alone (black bar, P = 0.0025). Data are expressed as the means of total cells recovered by lavage. Each point is the mean, with SEM shown by vertical bars.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2195693&req=5

Figure 11: Airway leukocyte populations were measured in bronchoalveolar lavage after pretreatment with AbIL5 and AbMBP. In nonsensitized virus-infected animals (black bars, n = 10), pretreatment with AbIL5 (gray bars, n = 5) did not change any of the leukocyte numbers (A). In contrast, pretreatment of sensitized virus-infected animals with AbIL5 (gray bars, n = 8) significantly decreased the number of eosinophils compared with sensitized virus-infected alone (black bars; n = 16, P < 0.0001) (B). Pretreatment of sensitized virus-infected animals with AbMBP (dark gray bars, n = 7) caused a slight but statistically significantly decrease in eosinophil numbers compared with sensitized virus-infected animals alone (black bars; n = 16, P = 0.04). In both AbIL5- and AbMBP-pretreated animals, neutrophil cell numbers were unaltered. Total leukocyte numbers were significantly decreased in sensitized virus-infected animals treated with AbIL5 (light gray bar) compared with sensitized virus-infected animals alone (black bar, P = 0.0025). Data are expressed as the means of total cells recovered by lavage. Each point is the mean, with SEM shown by vertical bars.

Mentions: Treatment with AbIL5 not did not change leukocyte numbers in the lavage fluid of nonsensitized virus-infected guinea pigs (Fig. 11 A.) In contrast, the total number of inflammatory cells in the sensitized virus-infected animals was decreased by AbIL5 (Fig. 11 B). This decrease was due to a significant decrease in eosinophils. Pretreatment with AbMBP caused a small but statistically significant decrease in the number of eosinophils recovered from the airways (Fig. 11 B). Neither AbIL5 nor AbMBP significantly altered the numbers of lymphocytes recovered in the lavage fluid.


Ovalbumin sensitization changes the inflammatory response to subsequent parainfluenza infection. Eosinophils mediate airway hyperresponsiveness, m(2) muscarinic receptor dysfunction, and antiviral effects.

Adamko DJ, Yost BL, Gleich GJ, Fryer AD, Jacoby DB - J. Exp. Med. (1999)

Airway leukocyte populations were measured in bronchoalveolar lavage after pretreatment with AbIL5 and AbMBP. In nonsensitized virus-infected animals (black bars, n = 10), pretreatment with AbIL5 (gray bars, n = 5) did not change any of the leukocyte numbers (A). In contrast, pretreatment of sensitized virus-infected animals with AbIL5 (gray bars, n = 8) significantly decreased the number of eosinophils compared with sensitized virus-infected alone (black bars; n = 16, P < 0.0001) (B). Pretreatment of sensitized virus-infected animals with AbMBP (dark gray bars, n = 7) caused a slight but statistically significantly decrease in eosinophil numbers compared with sensitized virus-infected animals alone (black bars; n = 16, P = 0.04). In both AbIL5- and AbMBP-pretreated animals, neutrophil cell numbers were unaltered. Total leukocyte numbers were significantly decreased in sensitized virus-infected animals treated with AbIL5 (light gray bar) compared with sensitized virus-infected animals alone (black bar, P = 0.0025). Data are expressed as the means of total cells recovered by lavage. Each point is the mean, with SEM shown by vertical bars.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2195693&req=5

Figure 11: Airway leukocyte populations were measured in bronchoalveolar lavage after pretreatment with AbIL5 and AbMBP. In nonsensitized virus-infected animals (black bars, n = 10), pretreatment with AbIL5 (gray bars, n = 5) did not change any of the leukocyte numbers (A). In contrast, pretreatment of sensitized virus-infected animals with AbIL5 (gray bars, n = 8) significantly decreased the number of eosinophils compared with sensitized virus-infected alone (black bars; n = 16, P < 0.0001) (B). Pretreatment of sensitized virus-infected animals with AbMBP (dark gray bars, n = 7) caused a slight but statistically significantly decrease in eosinophil numbers compared with sensitized virus-infected animals alone (black bars; n = 16, P = 0.04). In both AbIL5- and AbMBP-pretreated animals, neutrophil cell numbers were unaltered. Total leukocyte numbers were significantly decreased in sensitized virus-infected animals treated with AbIL5 (light gray bar) compared with sensitized virus-infected animals alone (black bar, P = 0.0025). Data are expressed as the means of total cells recovered by lavage. Each point is the mean, with SEM shown by vertical bars.
Mentions: Treatment with AbIL5 not did not change leukocyte numbers in the lavage fluid of nonsensitized virus-infected guinea pigs (Fig. 11 A.) In contrast, the total number of inflammatory cells in the sensitized virus-infected animals was decreased by AbIL5 (Fig. 11 B). This decrease was due to a significant decrease in eosinophils. Pretreatment with AbMBP caused a small but statistically significant decrease in the number of eosinophils recovered from the airways (Fig. 11 B). Neither AbIL5 nor AbMBP significantly altered the numbers of lymphocytes recovered in the lavage fluid.

Bottom Line: Asthma exacerbations, many of which are virus induced, are associated with airway eosinophilia.An additional and unexpected finding was that sensitization to ovalbumin caused a marked (80%) reduction in the viral content of the lungs.This was reversed by the antibody to IL-5, implicating a role for eosinophils in viral immunity.

View Article: PubMed Central - PubMed

Affiliation: Department of Environmental Health Sciences, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA.

ABSTRACT
Asthma exacerbations, many of which are virus induced, are associated with airway eosinophilia. This may reflect altered inflammatory response to viruses in atopic individuals. Inhibitory M(2) muscarinic receptors (M(2)Rs) on the airway parasympathetic nerves limit acetylcholine release. Both viral infection and inhalational antigen challenge cause M(2)R dysfunction, leading to airway hyperresponsiveness. In antigen-challenged, but not virus-infected guinea pigs, M(2)R dysfunction is due to blockade of the receptors by the endogenous antagonist eosinophil major basic protein (MBP). We hypothesized that sensitization to a nonviral antigen before viral infection alters the inflammatory response to viral infection, so that M(2)R dysfunction and hyperreactivity are eosinophil mediated. Guinea pigs were sensitized to ovalbumin intraperitoneally, and 3 wk later were infected with parainfluenza. In sensitized, but not in nonsensitized animals, virus-induced hyperresponsiveness and M(2)R dysfunction were blocked by depletion of eosinophils with antibody to interleukin (IL)-5 or treatment with antibody to MBP. An additional and unexpected finding was that sensitization to ovalbumin caused a marked (80%) reduction in the viral content of the lungs. This was reversed by the antibody to IL-5, implicating a role for eosinophils in viral immunity.

Show MeSH
Related in: MedlinePlus