Lactoferrin regulates an axis involving CD11b and CD49d integrins and the chemokines MIP-1α and MCP-1 in GM-CSF-treated human primary eosinophils.
Eosinophils are multifunctional immune cells that contribute to innate and adaptive immune/repair responses. Lactoferrin (LF) is an iron-binding protein indicated to alter cell adhesion and immune function by receptor-mediated interactions or by participating in redox mechanisms. The eosinophil adhesion molecules, αMβ2 and α4β1, are differentially expressed following exposure to the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) and various redox agents. We hypothesized that LF can alter the function and production of proteins involved in adhesion/migration. Utilizing eosinophil peroxidase activity or fluorescent labeling adhesion assays, LF reduced GM-CSF-induced eosinophil adhesion in the presence of fibronectin or vascular adhesion molecule-1 compared with GM-CSF treatment alone. Flow cytometric analysis of eosinophil αM (CD11b) and α4 (CD49d) integrins revealed that cotreatments (24 h) with LF plus GM-CSF induced a significant increase in CD11b compared with control and GM-CSF treatments but a significant decrease in CD49d compared with control and GM-CSF treatments. These changes in CD11b and CD49d levels were significantly correlated with the increased production of chemokines (macrophage inflammatory Protein-1α, monocyte chemotactic protein-1) and an identified increase in S100A9 production. Thus, LF release at sites of inflammation may alter eosinophil recruitment/activation and possibly the progression of diseases such as cancer and asthma where significant eosinophil influx has been described.
Department of Molecular Biology, University of Wisconsin, Madison, Wisconsin 53706, USA. colleen_curran@hotmail.com
Colleen S
CS
Curran
Paul J
PJ
Bertics
D006631:Amine Oxidase (Copper-Containing) / Q000378:metabolism; D039481:CD11b Antigen / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D054405:Chemokine CCL3 / Q000235:genetics / Q000378:metabolism*; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology*; D005353:Fibronectins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D039441:Integrin alpha4 / Q000235:genetics / Q000378:metabolism*; D007781:Lactoferrin / Q000494:pharmacology / Q000502:physiology*; D061251:Primary Cell Culture
C111835:CCL2 protein, human; D039481:CD11b Antigen; D015815:Cell Adhesion Molecules; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D005353:Fibronectins; D039441:Integrin alpha4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C076668:AOC3 protein, human; D006631:Amine Oxidase (Copper-Containing); D007781:Lactoferrin