Differential regulation of neutrophil CD18 integrin function by di- and tri-valent cations: manganese vs. gadolinium.

Y. Zhang, Heather N. Hayenga, Melissa R. Sarantos, Scott I. Simon, Sriram Neelamegham

Research output: Contribution to journalArticle

Abstract

Affinity regulation of integrin function plays an important role during both leukocyte-endothelial and leukocyte-leukocyte interactions. We compared the roles of Mn(2+) (Manganese) and Gd(3+) (Gadolinium) in regulating leukocyte CD18-integrin function. We observed that: (i) Both cations prolonged neutrophil homotypic aggregation following chemoattractant IL-8 stimulation, with Gd(3+) being effective at doses two orders of magnitude (10 microM range) lower that Mn(2+). (ii) While both Gd(3+) and Mn(2+) mediate homotypic cell aggregation via L: -selectin and CD18 integrins, their effects on the integrin subunits, LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18), was different. Gd(3+) altered both LFA-1 and Mac-1 function, while the dominant effect of Mn(2+) was on Mac-1. This effect of Gd(3+) on LFA-1 function was confirmed in cell-free studies that measured the binding of recombinant ICAM-1 to LFA-1 immobilized on beads. (iii) Both ions augmented the binding of 327C, an antibody that recognizes active CD18 on human neutrophils, both in the presence and absence of exogenous IL-8. The effects of Mn(2+) was more pronounced since it caused 3-4-fold increase in mAb 327C binding to neutrophils compared to Gd(3+) which increased antibody binding by only approximately 80%. 327C binding was partially reduced by Ca(2+). Further, 327C binding induced by Mn(2+) did not correlate tightly with cell adhesion function. (iv) In studies that monitored intracellular Ca(2+) ([Ca(2+)](i)), the addition of Mn(2+) but not Gd(3+) to neutrophils altered [Ca(2+)](i) levels. Overall, while both Gd(3+) and Mn(2+) stabilize high affinity CD18 mediated cell adhesion, Gd(3+) affects integrin conformation while Mn(2+) may also trigger other effects.

Original languageEnglish (US)
Pages (from-to)647-660
Number of pages14
JournalAnnals of Biomedical Engineering
Volume36
Issue number4
StatePublished - Apr 2008
Externally publishedYes

ASJC Scopus subject areas

  • Biomedical Engineering

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    Zhang, Y., Hayenga, H. N., Sarantos, M. R., Simon, S. I., & Neelamegham, S. (2008). Differential regulation of neutrophil CD18 integrin function by di- and tri-valent cations: manganese vs. gadolinium. Annals of Biomedical Engineering, 36(4), 647-660.