title: Inhibition of eosinophil migration by lactoferrin.
abstract: Eosinophilic granulocytes are innate effector cells that are important in immune responses against helminth parasitic infections and contribute towards the pathology associated with allergic inflammatory conditions, including allergic rhinitis and asthma. Their recruitment to inflammatory sites occurs in response to chemotactic and activation signals, such as eotaxin and interleukin-5, and is a tightly controlled process. However, the mechanisms that counterbalance these positive chemoattractive processes, thereby preventing excessive eosinophil infiltration, have received little attention. Here, we show that, lactoferrin (LTF), a pleiotropic 80-kDa glycoprotein with iron-binding properties, acts as a powerful inhibitor of eosinophil migration. Irrespective of its source (milk or neutrophil derived), LTF inhibits eotaxin-stimulated eosinophil migration with no effects on eosinophil viability. Transferrin, a closely related cationic glycoprotein, failed to produce an analogous effect. Furthermore, the iron-saturation status of LTF did not influence the observed inhibitory effect on migration, proving that LTF exerts its effect on eosinophil chemotaxis independent of its iron-chelating activity. These results highlight LTF as one of the few molecules reported to negatively regulate eosinophil migration. Thus, through its ability to inhibit eosinophil migration, LTF has potential as an effective therapeutic in the control of eosinophil infiltration in atopic inflammatory conditions.
authors.affiliation: Medical Research Council (MRC) Centre for Inflammation Research, Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, UK.
authors.forename: Irini
authors.initials: I
authors.lastname: Bournazou
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Mackenzie
authors.forename: Rodger
authors.initials: R
authors.lastname: Duffin
authors.forename: Adriano G
authors.initials: AG
authors.lastname: Rossi
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Gregory
mesh_terms: D054413:Chemokine CCL11 / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004804:Eosinophils / Q000166:cytology* / Q000187:drug effects*; D006801:Humans; D007501:Iron / Q000378:metabolism; D007781:Lactoferrin / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects
chemical_list: D054413:Chemokine CCL11; D007501:Iron; D007781:Lactoferrin