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

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

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Affinity regulation of integrin function plays an important role during both leukocyte-endothelial and leukocyte-leukocyte interactions. We compared the roles of Mn2+ (Manganese) and Gd3+ (Gadolinium) in regulating leukocyte CD18-integrin function. We observed that: (i) Both cations prolonged neutrophil homotypic aggregation following chemoattractant IL-8 stimulation, with Gd3+ being effective at doses two orders of magnitude (10 μM range) lower that Mn2+. (ii) While both Gd 3+ and Mn2+ 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. Gd3+ altered both LFA-1 and Mac-1 function, while the dominant effect of Mn2+ was on Mac-1. This effect of Gd3+ 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 Mn2+ was more pronounced since it caused 3-4-fold increase in mAb 327C binding to neutrophils compared to Gd3+ which increased antibody binding by only ̃80%. 327C binding was partially reduced by Ca2+. Further, 327C binding induced by Mn2+ did not correlate tightly with cell adhesion function. (iv) In studies that monitored intracellular Ca2+ ([Ca2+] i), the addition of Mn2+ but not Gd3+ to neutrophils altered [Ca2+]i levels. Overall, while both Gd3+ and Mn2+ stabilize high affinity CD18 mediated cell adhesion, Gd3+ affects integrin conformation while Mn2+ may also trigger other effects.

Original languageEnglish (US)
Pages (from-to)1-14
Number of pages14
JournalAnnals of Biomedical Engineering
DOIs
StatePublished - 2008

Keywords

  • 327C
  • CBRM1/5
  • Cell aggregation
  • Endothelium
  • Inflammation
  • Leukocyte
  • LFA-1
  • Mac-1

ASJC Scopus subject areas

  • Biomedical Engineering

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