EOSINOPHIL RECRUITMENT TO THE LUNG IN A MURINE MODEL OF ALLERGIC INFLAMMATION - THE ROLE OF T-CELLS, CHEMOKINES, AND ADHESION RECEPTORS

Eosinophil accumulation is a distinctive feature of lung allergic infl ammation, Here, we have used a mouse model of OVA (ovalbumin)-induced pulmonary eosinophilia to study the cellular and molecular mechanisms for this selective recruitment of eosinophils to the airways, In this model there was an early accumulation of infiltrating monocytes/macrop hages in the lung during the OVA treatment, whereas the increase in in filtrating T-lymphocytes paralleled the accumulation of eosinophils. T he kinetics of accumulation of these three leukocyte subtypes correlat ed with the levels of mRNA expression of the chemokines monocyte chemo tactic peptide-1/JE, eotaxin, and RANTES (regulated upon activation in normal T cells expressed and secreted), suggesting their involvement in the recruitment of these leukocytes, Furthermore, blockade of eotax in with specific antibodies in vivo reduced the accumulation of eosino phils in the lung in response to OVA by half, Mature CD4(+) T-lymphocy tes were absolutely required for OVA-induced eosinophil accumulation s ince lung eosinophilia was prevented in CD4(+)-deficient mice, However , these cells were neither the main producers of the major eosinophili c chemokines eotaxin, RANTES, or MIP-1 alpha, nor did they regulate th e expression of these chemokines, Rather, the presence of CD4(+) T cel ls was necessary for enhancement of VCAM-1 (vascular cell adhesion mol ecule-1) expression in the lung during allergic inflammation induced b y the OVA treatment, In support of this, mice genetically deficient fo r VCAM-1 and intercellular adhesion molecule-1 failed to develop pulmo nary eosinophilia, Selective eosinophilic recruitment during lung alle rgic inflammation results from a sequential accumulation of certain le ukocyte types, particularly T cells, and relies on the presence of bot h eosinophilic chemoattractants and adhesion receptors.