Hyaluronan levels in bronchoalveolar lavage of mice with induced allergic asthma

HAJOS SE; ERNST G; CORDO RUSSO R; LOMPARDÍA S; ALVAREZ E

Kobe

Congreso; 14º Congreso Internacional de Inmunología; 2010

Hyaluronan (HA) is an important constituent of the extracellular matrix, which accumulates during inflammatory lung disease like asthma. Low molecular weight (LMW-HA) but not high molecular weight HA (HMW-HA) have shown to induce inflammatory cytokines secretion. CD44 is its principal receptor. The aim of this work was to analyze the role of HA-CD44 interaction in asthma induced inflammation. For this purpose, we established a model of asthma by intranasal inoculation of Dermatophagoides pteronyssinus (Dp) in BALB/c mice, which produced a significant increase of eosinophils in bronchoalveolar lavage (BAL). Histochemical analysis showed that lungs of mice sensitized with Dp presented lymphoid infiltration associated to bronchial tissue, while control mice presented a normal structure. Flow cytometry analysis showed that the percentage of CD44+ cells in BAL was significantly increased in Dp treated mice compared to non-treated ones (47.4+3.6 vs. 14.0+7.1%, p,0.05). HA levels in BAL were measured by ELISA finding higher HA concentration in Dp treated animals compared to controls (5.68+1.58 vs. 0.51+0.11 ug/ml, p,0.05) while Dp mice pre-treated with either Budesonide or Dexametasone showed decreased HA levels (0.42+0.07 and 0.39+0.12 vs. 5.68+1.58 ug/ ml, p,0.05 respectively). Migratory capacity of cells from BAL was also evaluated showing that Dp sensitized mice presented higher migration towards LMW-HA as compared to RPMI (migration index 2.2+0.2 vs. 1) but not towards HMW-HA. When BAL cells were preincubated with anti-CD44 antibody, migration towards LMW-HA was inhibited (migration index 1.1+0.2). We conclude that HA-CD44 interaction is involved in inflammation induced by allergic asthma emphasizing its importance for therapy.