Molecular basis for selective eosinophil trafficking in asthma: A multistep paradigm.

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摘要：

Asthma is characterized by a 50- to 100-fold increase in the number of eosinophils relative to neutrophils in the bronchial mucosa. This increase is not the result of a single molecular event but of the cumulative and sequential effects of several approximately 4-fold increases in selective eosinophil versus neutrophil migration, occurring at a number of stages in the life cycle of the eosinophil. These steps include (1) effects on the bone marrow, mediated principally by IL-5, which result in a 4-fold increase in circulating eosinophils, (2) selective tethering of eosinophils to venular endothelium through the combined effects of P-selectin/P-selectin glycoprotein ligand 1 and very late activation antigen-4/vascular cell adhesion molecule-1, which has the potential for an up to 10-fold increase in eosinophil versus neutrophil adhesion, (3) selective chemotaxis under the influence of CC chemokines, and (4) prolonged survival, again mediated by IL-5. These events are integrated and directed by allergen-specific T H 2 lymphocytes through the generation of IL-5, IL-4, and IL-13. The implications of this multistep process are that antagonists of IL-5, very late activation antigen-4, P-selectin glycoprotein ligand 1, and CCR3 as well as IL-4 and IL-13 each have the potential to markedly inhibit eosinophil recruitment in asthma. (J Allergy Clin Immunol 1999;104:917-26.)

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Eosinophils migration adhesion chemotaxis asthma BAL , Bronchoalveolar lavage BHR , Bronchial hyperresponsiveness ECF-A , Eosinophil chemotactic factor of anaphylaxis FSA , Frozen section assay GC , Glucocorticoid HUVEC , Human umbilical vein endothelial cell ICAM , Intercellular adhesion molecule MCP , Monocyte chemotactic protein MIP , Macrophage inflammatory protein NPE , Nasal polyp endothelium PAF , Platelet-activating factor PSGL , P-selectin glycoprotein ligand 1 PT , Pertussis toxin VCAM , Vascular cell adhesion molecule VLA , Very late activation antigen