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 inflammation. 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/macrophages in the lung during the OVA treatment, whereas the increase in infiltrating T-lymphocytes paralleled the accumulation of eosinophils. The kinetics of accumulation of these three leukocyte subtypes correlated with the levels of mRNA expression of the chemokines monocyte chemotactic 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 eotaxin with specific antibodies in vivo reduced the accumulation of eosinophils in the lung in response to OVA by half. Mature CD4+ T-lymphocytes were absolutely required for OVA-induced eosinophil accumulation since lung eosinophilia was prevented in CD4+-deficient mice. However, these cells were neither the main producers of the major eosinophilic chemokines eotaxin, RANTES, or MIP-1alpha, nor did they regulate the expression of these chemokines. Rather, the presence of CD4+ T cells was necessary for enhancement of VCAM-1 (vascular cell adhesion molecule-1) expression in the lung during allergic inflammation induced by the OVA treatment. In support of this, mice genetically deficient for VCAM-1 and intercellular adhesion molecule-1 failed to develop pulmonary eosinophilia. Selective eosinophilic recruitment during lung allergic inflammation results from a sequential accumulation of certain leukocyte types, particularly T cells, and relies on the presence of both eosinophilic chemoattractants and adhesion receptors.
Gonzalo
J A
JA
The Center for Blood Research, Inc., The Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
Lloyd
C M
CM
Kremer
L
L
Finger
E
E
Martinez-A
C
C
Siegelman
M H
MH
Cybulsky
M
M
Gutierrez-Ramos
J C
JC
D000818:Animals; D019138:Antibodies, Blocking / Q000276:immunology; D001402:B-Lymphocytes / Q000502:physiology; D015152:Blotting, Northern; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D002465:Cell Movement; D054413:Chemokine CCL11; D018932:Chemokine CCL2 / Q000096:biosynthesis; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000096:biosynthesis; D019742:Chemokines, CC; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004802:Eosinophilia / Q000235:genetics / Q000276:immunology*; D005260:Female; D016867:Immunocompromised Host / Q000235:genetics; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D019041:L-Selectin / Q000502:physiology; D008168:Lung / Q000276:immunology*; D008231:Lymphopenia / Q000235:genetics; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis; D008264:Macrophages / Q000276:immunology / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010047:Ovalbumin / Q000276:immunology; D019007:P-Selectin / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D012130:Respiratory Hypersensitivity / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology
D019138:Antibodies, Blocking; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019742:Chemokines, CC; D016207:Cytokines; D019402:Macrophage Inflammatory Proteins; D019007:P-Selectin; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D019041:L-Selectin; D010047:Ovalbumin