Cell-specific, activation-dependent regulation of neutrophil CD32A ligand-binding function

Shanmugam Nagarajan, Kala Venkiteswaran, Michael Anderson, Umar Sayed, Cheng Zhu, Periasamy Selvaraj

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Neutrophils express 2 low-affinity FcγR, FcγRIIIB (CD16B), and FcγRIIA (CD32A). CD16B is a glycosyl-phosphatidyl inositol-anchored molecule, whereas CD32A is a polypeptide-anchored molecule. These 2 receptors also differ in their signaling. The biological significance of coexpression of 2 FcγRs with distinct membrane anchors and signaling capacities is not clearly understood. Using neutrophils from a CD16B-deficient donor and normal neutrophils treated with anti-CD16 monoclonal antibodies, the authors demonstrated that affinity modulation of CD32A is one of the mechanisms by which neutrophils regulate their FcγR-dependent functions. Neutrophils isolated from a CD16B- donor rosetted poorly with sheep erythrocytes opsonized with rabbit IgG (EA) (12% ± 2% versus 80% ± 6% for control) and were unable to mediate immunophagocytosis. However, activation of CD16B- neutrophils with fMLP, a bacterial chemotactic peptide, increased the CD32A- dependent EA rosetting to 58%. The CD32A-dependent rosetting of fMLP- activated normal neutrophils also increased nearly 5-fold, but there was no increase in CD32A expression. The CD32A-dependent immune complex (IC) binding was also increased in activated neutrophils. This affinity regulation was not observed with CD32A expressed on Chinese hamster ovary cells. These results suggest that in resting neutrophils CD32A is in a low-affinity state and that these cells primarily engage CD16B for IC binding. However, once the neutrophils are activated, the CD32A is converted to a high-affinity state that leads to CD32A-dependent ligand binding and signaling. These results suggest that neutrophils adopt a novel strategy to engage the 2 different FcγR selectively during physiologic and pathologic conditions to carry out their functions efficiently.

Original languageEnglish (US)
Pages (from-to)1069-1077
Number of pages9
JournalBlood
Volume95
Issue number3
StatePublished - Feb 1 2000

Fingerprint

Neutrophils
Chemical activation
Ligands
Antigen-Antibody Complex
Peptides
Molecules
Phosphatidylinositols
Anchors
Immunoglobulin G
Monoclonal Antibodies
Cells
Modulation
Membranes
Neutrophil Activation
Cricetulus
Ovary
Sheep
Erythrocytes
Rabbits

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Nagarajan, S., Venkiteswaran, K., Anderson, M., Sayed, U., Zhu, C., & Selvaraj, P. (2000). Cell-specific, activation-dependent regulation of neutrophil CD32A ligand-binding function. Blood, 95(3), 1069-1077.
Nagarajan, Shanmugam ; Venkiteswaran, Kala ; Anderson, Michael ; Sayed, Umar ; Zhu, Cheng ; Selvaraj, Periasamy. / Cell-specific, activation-dependent regulation of neutrophil CD32A ligand-binding function. In: Blood. 2000 ; Vol. 95, No. 3. pp. 1069-1077.
@article{d9775fdefb064df183e76d6729b81dd1,
title = "Cell-specific, activation-dependent regulation of neutrophil CD32A ligand-binding function",
abstract = "Neutrophils express 2 low-affinity FcγR, FcγRIIIB (CD16B), and FcγRIIA (CD32A). CD16B is a glycosyl-phosphatidyl inositol-anchored molecule, whereas CD32A is a polypeptide-anchored molecule. These 2 receptors also differ in their signaling. The biological significance of coexpression of 2 FcγRs with distinct membrane anchors and signaling capacities is not clearly understood. Using neutrophils from a CD16B-deficient donor and normal neutrophils treated with anti-CD16 monoclonal antibodies, the authors demonstrated that affinity modulation of CD32A is one of the mechanisms by which neutrophils regulate their FcγR-dependent functions. Neutrophils isolated from a CD16B- donor rosetted poorly with sheep erythrocytes opsonized with rabbit IgG (EA) (12{\%} ± 2{\%} versus 80{\%} ± 6{\%} for control) and were unable to mediate immunophagocytosis. However, activation of CD16B- neutrophils with fMLP, a bacterial chemotactic peptide, increased the CD32A- dependent EA rosetting to 58{\%}. The CD32A-dependent rosetting of fMLP- activated normal neutrophils also increased nearly 5-fold, but there was no increase in CD32A expression. The CD32A-dependent immune complex (IC) binding was also increased in activated neutrophils. This affinity regulation was not observed with CD32A expressed on Chinese hamster ovary cells. These results suggest that in resting neutrophils CD32A is in a low-affinity state and that these cells primarily engage CD16B for IC binding. However, once the neutrophils are activated, the CD32A is converted to a high-affinity state that leads to CD32A-dependent ligand binding and signaling. These results suggest that neutrophils adopt a novel strategy to engage the 2 different FcγR selectively during physiologic and pathologic conditions to carry out their functions efficiently.",
author = "Shanmugam Nagarajan and Kala Venkiteswaran and Michael Anderson and Umar Sayed and Cheng Zhu and Periasamy Selvaraj",
year = "2000",
month = "2",
day = "1",
language = "English (US)",
volume = "95",
pages = "1069--1077",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "3",

}

Nagarajan, S, Venkiteswaran, K, Anderson, M, Sayed, U, Zhu, C & Selvaraj, P 2000, 'Cell-specific, activation-dependent regulation of neutrophil CD32A ligand-binding function', Blood, vol. 95, no. 3, pp. 1069-1077.

Cell-specific, activation-dependent regulation of neutrophil CD32A ligand-binding function. / Nagarajan, Shanmugam; Venkiteswaran, Kala; Anderson, Michael; Sayed, Umar; Zhu, Cheng; Selvaraj, Periasamy.

In: Blood, Vol. 95, No. 3, 01.02.2000, p. 1069-1077.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Cell-specific, activation-dependent regulation of neutrophil CD32A ligand-binding function

AU - Nagarajan, Shanmugam

AU - Venkiteswaran, Kala

AU - Anderson, Michael

AU - Sayed, Umar

AU - Zhu, Cheng

AU - Selvaraj, Periasamy

PY - 2000/2/1

Y1 - 2000/2/1

N2 - Neutrophils express 2 low-affinity FcγR, FcγRIIIB (CD16B), and FcγRIIA (CD32A). CD16B is a glycosyl-phosphatidyl inositol-anchored molecule, whereas CD32A is a polypeptide-anchored molecule. These 2 receptors also differ in their signaling. The biological significance of coexpression of 2 FcγRs with distinct membrane anchors and signaling capacities is not clearly understood. Using neutrophils from a CD16B-deficient donor and normal neutrophils treated with anti-CD16 monoclonal antibodies, the authors demonstrated that affinity modulation of CD32A is one of the mechanisms by which neutrophils regulate their FcγR-dependent functions. Neutrophils isolated from a CD16B- donor rosetted poorly with sheep erythrocytes opsonized with rabbit IgG (EA) (12% ± 2% versus 80% ± 6% for control) and were unable to mediate immunophagocytosis. However, activation of CD16B- neutrophils with fMLP, a bacterial chemotactic peptide, increased the CD32A- dependent EA rosetting to 58%. The CD32A-dependent rosetting of fMLP- activated normal neutrophils also increased nearly 5-fold, but there was no increase in CD32A expression. The CD32A-dependent immune complex (IC) binding was also increased in activated neutrophils. This affinity regulation was not observed with CD32A expressed on Chinese hamster ovary cells. These results suggest that in resting neutrophils CD32A is in a low-affinity state and that these cells primarily engage CD16B for IC binding. However, once the neutrophils are activated, the CD32A is converted to a high-affinity state that leads to CD32A-dependent ligand binding and signaling. These results suggest that neutrophils adopt a novel strategy to engage the 2 different FcγR selectively during physiologic and pathologic conditions to carry out their functions efficiently.

AB - Neutrophils express 2 low-affinity FcγR, FcγRIIIB (CD16B), and FcγRIIA (CD32A). CD16B is a glycosyl-phosphatidyl inositol-anchored molecule, whereas CD32A is a polypeptide-anchored molecule. These 2 receptors also differ in their signaling. The biological significance of coexpression of 2 FcγRs with distinct membrane anchors and signaling capacities is not clearly understood. Using neutrophils from a CD16B-deficient donor and normal neutrophils treated with anti-CD16 monoclonal antibodies, the authors demonstrated that affinity modulation of CD32A is one of the mechanisms by which neutrophils regulate their FcγR-dependent functions. Neutrophils isolated from a CD16B- donor rosetted poorly with sheep erythrocytes opsonized with rabbit IgG (EA) (12% ± 2% versus 80% ± 6% for control) and were unable to mediate immunophagocytosis. However, activation of CD16B- neutrophils with fMLP, a bacterial chemotactic peptide, increased the CD32A- dependent EA rosetting to 58%. The CD32A-dependent rosetting of fMLP- activated normal neutrophils also increased nearly 5-fold, but there was no increase in CD32A expression. The CD32A-dependent immune complex (IC) binding was also increased in activated neutrophils. This affinity regulation was not observed with CD32A expressed on Chinese hamster ovary cells. These results suggest that in resting neutrophils CD32A is in a low-affinity state and that these cells primarily engage CD16B for IC binding. However, once the neutrophils are activated, the CD32A is converted to a high-affinity state that leads to CD32A-dependent ligand binding and signaling. These results suggest that neutrophils adopt a novel strategy to engage the 2 different FcγR selectively during physiologic and pathologic conditions to carry out their functions efficiently.

UR - http://www.scopus.com/inward/record.url?scp=0034142338&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034142338&partnerID=8YFLogxK

M3 - Article

VL - 95

SP - 1069

EP - 1077

JO - Blood

JF - Blood

SN - 0006-4971

IS - 3

ER -

Nagarajan S, Venkiteswaran K, Anderson M, Sayed U, Zhu C, Selvaraj P. Cell-specific, activation-dependent regulation of neutrophil CD32A ligand-binding function. Blood. 2000 Feb 1;95(3):1069-1077.