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 by intraperitoneal injection of ovalbumin and aluminum hydroxide and serial exposure to aerosols of ovalbumin. Mice lacking a functioning 5-lipoxygenase enzyme were produced by targeted gene disruption. They and their wild-type controls had measurements of lung resistance (RL) made in response to intravenous methacholine; bronchoalveolar lavage fluid cell counts and serum immunoglobulin concentrations were also measured. Wild-type mice developed striking increases in cholinergic responsiveness; 5-lipoxygenase-deficient mice manifested minimal alterations in methacholine responsiveness (RL at the highest methacholine dose was 9.9 +/- 2.4 cmH2O.ml-1.s-1 under control conditions vs. 27.6 +/- 4.6 cmH2O.ml-1.s-1 after ovalbumin in wild-type mice; 5.9 +/- 0.9 vs. 7.01 +/- 2.2 cmH2O.ml-1.s-1 in 5-lipoxygenase-deficient mice). Ovalbumin provoked airway eosinophilia and increased immunoglobulins in wild-type mice, which were present to a significantly lesser degree in 5-lipoxygenase-deficient mice. We conclude that 5-lipoxygenase products are essential for the production of nonspecific airway reactivity in mice and suggest that 5-lipoxygenase products may be important in immunoglobulin formation.
Irvin
C G
CG
Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206, USA.
Tu
Y P
YP
Sheller
J R
JR
Funk
C D
CD
D000336:Aerosols; D000704:Analysis of Variance; D000818:Animals; D000917:Antibody Formation; D001094:Arachidonate 5-Lipoxygenase / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D016535:Bronchial Hyperreactivity / Q000235:genetics / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000097:blood; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D007962:Leukocytes / Q000276:immunology; D008168:Lung / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology*; D012129:Respiratory Function Tests
D000336:Aerosols; D007074:Immunoglobulin G; D016210:Methacholine Chloride; D007073:Immunoglobulin E; D010047:Ovalbumin; D001094:Arachidonate 5-Lipoxygenase