AIRWAY RESPONSIVENESS IN 2 INBRED STRAINS OF MOUSE DISPARATE IN IGE AND IL-4 PRODUCTION

The mouse provides an excellent model for genetic studies of asthma, w hich is characterized by airway hyperexcitability and hyperreactivity, The former is a function of the properties of the membrane of the air way smooth muscle (ASM), whereas the latter is a function, albeit indi rectly, of the mechanical properties of the muscle contractile apparat us, The very small size of the muscle has in the past hampered its stu dy, We report herein that contractile properties of tracheal smooth mu scle (TSM) can be measured in mice, We examined TSM strips from two in bred strains of mouse, ASW and SJL, which are high and low IgE respond ers, respectively. Force-velocity relationships were measured in four groups of mice, two ASW (control and sensitized) and two SJL (control and sensitized), Muscle strips from sensitized SJL mice exhibited shor tening velocities (V-0) and maximum shortening capacities (Delta L-max ), that were significantly greater than those of the other groups. Ho Never, no difference was found between the two strains in maximal isom etric force (Pal, The two strains also showed differences in their pot ential to express cytokines such as interleukin-4 (IL-4) and IL-5 in e x vivo splenocyte cultures, as measured by the cytokines' messenger RN A (mRNA) and protein expression. The SJL strain, which exhibited TSM h yperreactivity, was found to produce significantly greater amounts of IL-4 than the ASW strain. We conclude that the altered contractile pro perties of TSM in sensitized SJL mice are independent of IgE response, but linked to increased amounts of IL-4.