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 language | English (US) |
|---|---|
| Pages (from-to) | 1-14 |
| Number of pages | 14 |
| Journal | Annals of Biomedical Engineering |
| DOIs | |
| State | Published - 2008 |
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Keywords
- 327C
- CBRM1/5
- Cell aggregation
- Endothelium
- Inflammation
- Leukocyte
- LFA-1
- Mac-1
ASJC Scopus subject areas
- Biomedical Engineering
Cite this
Differential regulation of neutrophil CD18 integrin function by di- and tri-valent cations : Manganese vs. Gadolinium. / Zhang, Yi; Hayenga, Heather N.; Sarantos, Melissa R.; Simon, Scott I.; Neelamegham, Sriram.
In: Annals of Biomedical Engineering, 2008, p. 1-14.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Differential regulation of neutrophil CD18 integrin function by di- and tri-valent cations
T2 - Manganese vs. Gadolinium
AU - Zhang, Yi
AU - Hayenga, Heather N.
AU - Sarantos, Melissa R.
AU - Simon, Scott I.
AU - Neelamegham, Sriram
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
KW - 327C
KW - CBRM1/5
KW - Cell aggregation
KW - Endothelium
KW - Inflammation
KW - Leukocyte
KW - LFA-1
KW - Mac-1
UR - http://www.scopus.com/inward/record.url?scp=40949166187&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=40949166187&partnerID=8YFLogxK
U2 - 10.1007/s10439-008-9446-7
DO - 10.1007/s10439-008-9446-7
M3 - Article
AN - SCOPUS:40949166187
SP - 1
EP - 14
JO - Annals of Biomedical Engineering
JF - Annals of Biomedical Engineering
SN - 0090-6964
ER -