Anti-D initially stimulates an Fc-dependent leukocyte oxidative burst and subsequently suppresses erythrophagocytosis via interleukin-1 receptor antagonist
(2003) In Blood 102(8). p.2862-2867- Abstract
Previous results have demonstrated that anti-D therapy in children with chronic autoimmune thrombocytopenic purpura (AITP) induced a significant increase in several pro- and anti-inflammatory plasma cytokines within 2 hours of administration. To investigate the biologic basis of these early in vivo responses, we developed a flow cytometric assay to measure Fc-dependent responses of human peripheral leukocytes with fluorescently labeled and anti-D-opsonized red blood cells (RBCs). When anti-D-opsonized RBCs were incubated with peripheral blood leukocytes, the earliest detectible event observed was a significant oxidative burst in both monocytes (P < .05) and granulocytes (P < .0001), characterized by the production of hydrogen... (More)
Previous results have demonstrated that anti-D therapy in children with chronic autoimmune thrombocytopenic purpura (AITP) induced a significant increase in several pro- and anti-inflammatory plasma cytokines within 2 hours of administration. To investigate the biologic basis of these early in vivo responses, we developed a flow cytometric assay to measure Fc-dependent responses of human peripheral leukocytes with fluorescently labeled and anti-D-opsonized red blood cells (RBCs). When anti-D-opsonized RBCs were incubated with peripheral blood leukocytes, the earliest detectible event observed was a significant oxidative burst in both monocytes (P < .05) and granulocytes (P < .0001), characterized by the production of hydrogen peroxide (H2O2), peroxynitrite (ONOO-), superoxide (O2-), and hydroxyl (OH) by 10 minutes which declined by 1 hour. By 2 hours, the opsonized RBCs were phagocytosed, particularly by granulocytes (P < .001), but the phagocytosis subsequently declined by 6 hours of incubation. The decline in phagocytosis was correlated with a significant production of interleukin-1 receptor antagonist (IL1ra) by both monocytes (P = .036) and granulocytes (P = .0002) within 4 hours. None of these events occurred if the RBCs were coated with anti-D F(ab)′ 2 fragments. When recombinant IL1ra was titrated into the assay, phagocytosis of the opsonized RBCs was significantly inhibited (P = .002). Taken together, these results suggest that at least one mechanism of action of anti-D is via the production of the anti-inflammatory cytokine IL1ra which can negatively regulate the ability of leukocytes to phagocytose opsonized cells.
(Less)
- author
- Coopamah, Malini D. ; Freedman, John and Semple, John W. LU
- publishing date
- 2003-10-15
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Blood
- volume
- 102
- issue
- 8
- pages
- 2862 - 2867
- publisher
- American Society of Hematology
- external identifiers
-
- pmid:12829590
- scopus:0141889306
- ISSN
- 0006-4971
- DOI
- 10.1182/blood-2003-04-1029
- language
- English
- LU publication?
- no
- id
- 80a84805-c615-459d-acd9-7b9b8c6693f6
- date added to LUP
- 2019-12-03 10:23:37
- date last changed
- 2024-01-02 01:04:54
@article{80a84805-c615-459d-acd9-7b9b8c6693f6,
abstract = {{<p>Previous results have demonstrated that anti-D therapy in children with chronic autoimmune thrombocytopenic purpura (AITP) induced a significant increase in several pro- and anti-inflammatory plasma cytokines within 2 hours of administration. To investigate the biologic basis of these early in vivo responses, we developed a flow cytometric assay to measure Fc-dependent responses of human peripheral leukocytes with fluorescently labeled and anti-D-opsonized red blood cells (RBCs). When anti-D-opsonized RBCs were incubated with peripheral blood leukocytes, the earliest detectible event observed was a significant oxidative burst in both monocytes (P < .05) and granulocytes (P < .0001), characterized by the production of hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>), peroxynitrite (ONOO<sup>-</sup>), superoxide (O<sub>2</sub><sup>-</sup>), and hydroxyl (OH) by 10 minutes which declined by 1 hour. By 2 hours, the opsonized RBCs were phagocytosed, particularly by granulocytes (P < .001), but the phagocytosis subsequently declined by 6 hours of incubation. The decline in phagocytosis was correlated with a significant production of interleukin-1 receptor antagonist (IL1ra) by both monocytes (P = .036) and granulocytes (P = .0002) within 4 hours. None of these events occurred if the RBCs were coated with anti-D F(ab)′ <sub>2</sub> fragments. When recombinant IL1ra was titrated into the assay, phagocytosis of the opsonized RBCs was significantly inhibited (P = .002). Taken together, these results suggest that at least one mechanism of action of anti-D is via the production of the anti-inflammatory cytokine IL1ra which can negatively regulate the ability of leukocytes to phagocytose opsonized cells.</p>}},
author = {{Coopamah, Malini D. and Freedman, John and Semple, John W.}},
issn = {{0006-4971}},
language = {{eng}},
month = {{10}},
number = {{8}},
pages = {{2862--2867}},
publisher = {{American Society of Hematology}},
series = {{Blood}},
title = {{Anti-D initially stimulates an Fc-dependent leukocyte oxidative burst and subsequently suppresses erythrophagocytosis via interleukin-1 receptor antagonist}},
url = {{http://dx.doi.org/10.1182/blood-2003-04-1029}},
doi = {{10.1182/blood-2003-04-1029}},
volume = {{102}},
year = {{2003}},
}