[Inflammatory memory of pulmonary local lymphocytes in asthmatic mice].

OBJECTIVE

To investigate if long-lived inflammatory memory exists in the airway of asthmatic mice, and whether pulmonary local lymphocytes could transfer the inflammatory memory.

METHODS

97 mice were divided into six groups by random number meter: asthma group (group A, n = 50), long term group (group B, n = 20), control group of long term (group C, n = 6), adoptive transfer group (group D, n = 12, subgroups D1, D2 and D3 divided based on the transferred cells counts), adoptive transfer control group (group E, n = 6), and naive group( group F, n = 3). There were subgroups using BSA (bovine serum album) substituting OVA (ovalbumin) for the second challenge, named subgroup B-BSA in group B and subgroup D-BSA in group D. Pathologic changes, alveolar eosinophil infiltration, total cell counts (TCC) in bronchoalveolar lavage fluid (BALF), leukocyte differentials, and BALF IL-5 level were assayed in every group. Comparisons of inflammation responses between group B and group A, also between group D and group A were made. From asthmatic mice 34 d post aerosol, bronchoalveolar lavage (BAL) cells and splenocytes free of red blood cells (NR-splenocyte in brief) were cultured in vitro and stimulated with allergens, to detect cell proliferations and IL-5 levels in the supernatant.

RESULTS

(1) Vasculitis, alveolitis and bronchiolitis were observed in group A. TCC, BALF eosinophil and IL-5 reached peak on 240 h and 8 h, 24 h post aerosol respectively [ (22 +/- 5 ) x 10(4)/ml, (1.43 +/- 0.09) x 10(4)/ml and (75.1 +/- 52. 9) pg/ml, respectively]. There were scattered vasculitis and al)veolitis in group B before second OVA challenge; and more severe vasculitis and 3-fold higher alveolitis (ratio of alveolar eosinophil inflammation indexes is 21.23/7.14) were observed after second challenge. TCC and BALF eosinophils reached peak 24 h post aerosol [(121.5 +/- 19.1) x 10(4)/ml and (12.960 +/- 2.040) x 10(4)/ml respectively], BALF IL-5 reached to its highest level [(50.8 +/- 18.5) pg/ml] 48 h post aerosol. There were mild vasculitis in group B-BSA, while TCC [(5.3 +/- 2. 1) x 10(4)/ml] and eosinophil [(0.060 +/- 0. 050) x 10(4)/ml] were both significantly lower than those of group B 24 h post aerosol [(121.5 +/- 19. 1 ) x 10(4)/ml and (12.960 +/- 2.040) x 10(4)/ml respectively, P < 0.05]. BAL cells stimulated with OVA in vitro proliferated stronger [(166.8 +/- 4.81) Bq] than those with BSA stimulation [(61.0 +/- 24.1) Bq] (P < 0.05). Supernatant IL-5 levels in cell cultures with OVA or BSA stimulation were similar [(49 +/- 4) pg/ml and (46 +/- 21) pg/ml respectively] (P > 0.05). (2) There were vasculitis in group D2, with TCC [(5.0 +/- 1.0) x 10(4)/ml] and BALF IL-5 [(24.4 +/- 2.1) pg/ml] 24 h post aerosol. There were bronchiolitis in group D3, with TCC [(7.3 +/- 5.8) x 10(4)/ml] and BALF IL-5 [(45 +/- 6.2) pg/ml] 24 h post aerosol. There was significant difference between group D2 and D3 on BALF IL-5 (P < 0. 05), but not on TCC (P > 0. 05). No vasculitis was observed in group D-BSA, with TCC [(3.3 +/- 4.2) x 10(4)/ml] not statistically different from group D [(5.0 +/- 1.0) x 10(4)/ml] (P > 0. 05).

CONCLUSION

It is illustrated that long-lived inflammatory memory may exist in asthmatic mice lung, and pulmonary local lymphocytes may sufficient to transfer the memory.