Priming of eosinophil migration across lung epithelial cell monolayers and upregulation of CD11b/CD18 are elicited by extracellular Ca2+.
In patients with asthma, eosinophils are primed and massively infiltrate lung tissues and migrate across epithelia into airways. Using blocking monoclonal antibodies, we found that eosinophil transmigration across a lung epithelial cell monolayer depended on the functions of alphaMbeta2 integrin CD11b/CD18. To study the role of Ca2+ in eosinophil priming and transepithelial migration, we treated eosinophils with eotaxin or thapsigargin (TG), reagents that increase cytoplasmic free Ca2+ concentrations by receptor- or nonreceptor-mediated mechanisms, respectively. Pretreatment of eosinophils with TG enhanced CD11b/CD18-dependent transmigration across lung epithelium. Within minutes, TG time- and dose-dependently upregulated the expression of CD11b/CD18 but did not upregulate the expression of alphaL (CD11a) or beta1 (CD29) integrin. The upregulation of CD11b/CD18 expression by eotaxin or TG was prevented when Ca2+ entry was blocked. The priming of eosinophil transmigration by TG was also abrogated by the blockade of Ca2+ entry. Our results indicate that induction of Ca2+ entry by the depletion of Ca2+ from intracellular stores upregulates CD11b/CD18 expression on eosinophils and primes eosinophil transmigration across lung epithelium. Both responses are therefore elicited by extracellular Ca2+. We suggest that, as an important priming signal for human eosinophil functional responses, store-operated Ca2+ entry may be one of the underlying mechanisms of eosinophilic inflammation in asthma.
Liu
Lixin
L
Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden. lixliu@ucalgary.ca
Hakansson
Lena
L
Ridefelt
Peter
P
Garcia
Rodolfo C
RC
Venge
Per
P
D039481:CD11b Antigen / Q000378:metabolism*; D018821:CD18 Antigens / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000494:pharmacology; D002631:Chemotactic Factors, Eosinophil / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004804:Eosinophils / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D005110:Extracellular Space; D006801:Humans; D007811:Lanthanum / Q000494:pharmacology; D008168:Lung / Q000166:cytology / Q000276:immunology; D019284:Thapsigargin / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
C515456:CCL11 protein, human; D039481:CD11b Antigen; D018821:CD18 Antigens; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil; D004791:Enzyme Inhibitors; D019284:Thapsigargin; D007811:Lanthanum; D002118:Calcium