5-LIPOXYGENASE PRODUCTS ARE NECESSARY FOR OVALBUMIN-INDUCED AIRWAY RESPONSIVENESS IN MICE

To determine the role of 5-lipoxygenase products in the development of airway reactivity that follows antigen exposure, we sensitized mice b y intraperitoneal injection of ovalbumin and aluminum hydroxide and se rial exposure to aerosols of ovalbumin. Mice lacking a functioning B-l ipoxygenase enzyme were produced by targeted gene disruption. They and their wild-type controls had measurements of lung resistance (R-L) ma de in response to intravenous methacholine; bronchoalveolar lavage flu id cell counts and serum immunoglobulin concentrations were also measu red. Wildtype mice developed striking increases in cholinergic respons iveness; 5-lipoxygenase-deficient mice manifested minimal alterations in methacholine responsiveness (R-L at the highest methacholine dose w as 9.9 +/- 2.4 cmH(2)O . ml(-1).s(-1) under control conditions vs. 27. 6 +/- 4.6 cmH(2)O . ml(-1).s(-1) after ovalbumin in wild-type mice; 5. 9 +/- 0.9 vs. 7.01 +/- 2.2 cmH(2)O . ml(-1).s(-1) in 5-lipoxygenase-de ficient mice). Ovalbumin provoked airway eosinophilia and increased im munoglobulins in wild-type mice, which were present to a significantly lesser degree in 5-lipoxygenase-deficient mice. We conclude that 5-li poxygenase products are essential for the production of nonspecific ai rway reactivity in mice and suggest that 5-lipoxygenase products may b e important in immunoglobulin formation.