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New factor implicated in allergy and asthma attacks

apas Hazra, Sankar Mitra, Randall Goldblum and Sanjiv Sur and Rafeul Alam (formerly of UTMB and now director of the Division of Allergy and Immunology at the National Jewish Medical and Research Center in Denver)--worked nearly four years conducting extensive test-tube and lab-mouse experiments to prove the paradigm-shifting "two-signal concept" in detail. They zeroed in on a key enzyme known as NADPH oxidase, which they identified in grains of pollen produced by ragweed and 38 other plant pollens and molds linked to allergy and asthma attacks. Within minutes of exposure, ragweed pollen or its extract containing NADPH oxidase produce damaging reactive oxygen species in cell culture and, in experiments with mice, in their lungs and airway lining fluid. The resulting oxidative stress, Boldogh said, almost immediately prompted the production of inflammatory immune signaling molecules and accumulation of inflammatory cells, a downstream event common to lung and other type of allergic inflammations. By contrast, ragweed pollen extract from which NADPH oxidase had been removed produced no reactive oxygen species, and resulted in a much smaller increase in numbers of inflammatory immune cells.

"We showed that you need both oxidative stress and antigenic exposure to get a robust allergy or asthma attack, and also that the first few minutes of the exposure are critical," Boldogh said. "The antigen exposure has to happen in parallel with oxidative stress, and having both components in the pollen makes that possible." These two signals play a vital role in inducing allergic inflammation.

These findings suggest that antioxidant substances may be useful in forestalling allergy or asthma attacks. Sur and Boldogh predict that this new paradigm of initiation of allergic inflammation will lead to extensive research into discovery of novel compounds that either specifically inhibit pollen NADPH oxidases or those that prevent or inhibit oxidative stress in the lungs in
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Source:University of Texas Medical Branch at Galveston


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