Human alloantibody anti-Mart interferes with Mac-1-dependent leukocyte adhesion

Ulrich J H Sach; Triantafyllos Chavakis; Yoke Lin Fung; Alexander Lohrenz; Jurgen Bux; Angelika Reil; Andreas Ruf; Sentot Santoso

doi:10.1182/blood-2003-11-3809

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Human alloantibody anti-Mart interferes with Mac-1-dependent leukocyte adhesion

Journal article

Peer reviewed

Human alloantibody anti-Mart interferes with Mac-1-dependent leukocyte adhesion

Ulrich J H Sach, Triantafyllos Chavakis, Yoke Lin Fung, Alexander Lohrenz, Jurgen Bux, Angelika Reil, Andreas Ruf and Sentot Santoso

Blood, Vol.104(3), pp.727-734

2004

DOI: https://doi.org/10.1182/blood-2003-11-3809

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Abstract

Cardiovascular Medicine and Haematology

Clinical Sciences

Paediatrics and Reproductive Medicine

The CD11b/CD18 integrin plays a crucial role in cell-cell adhesion processes. Recently, we described a case of severe neonatal alloimmune neutropenia (NAIN) caused by an alloantibody against a variant of the CD11b subunit (Mart alloantigen). Allele-specific transfected cells allowed us to demonstrate that an H61R point mutation is directly responsible for the formation of Mart epitopes. No difference in the adhesion capability between H61 and R61 homozygous neutrophils was observed. Functional analysis showed that anti-Mart inhibited Mac-1-dependent adhesion of neutrophils and monocytic U937 cells to fibrinogen, intercellular adhesion molecule-1 (ICAM-1), receptor for advanced glycation end product (RAGE), and glycoprotein Ibα but not to junctional adhesion molecule-C or urokinase plasminogen activator receptor (uPAR). Accordingly, anti-Mart blocked neutrophil and U937 cell adhesion to endothelial cells and platelet-leukocyte aggregate formation in whole blood under high shear. Other sera of anti-Mart from mothers of infants without NAIN did not show inhibitory properties. We conclude that anti-Mart antibodies with different functional properties exist. This is supported by our findings that anti-Mart antibodies have different abilities to inhibit cell-cell adhesion, to enhance the respiratory burst of neutrophils, and to recognize different epitopes at the N-terminal region of CD11b. In conclusion, some anti-Mart alloantibodies interfere with Mac-1-dependent cellular functions of neutrophils, cause NAIN, and may be used as tools for studying Mac-1-dependent functions.

Details

Title: Human alloantibody anti-Mart interferes with Mac-1-dependent leukocyte adhesion
Authors: Ulrich J H Sach (Author)
Triantafyllos Chavakis (Author)
Yoke Lin Fung (Author) - Australian Red Cross Blood Service
Alexander Lohrenz (Author)
Jurgen Bux (Author)
Angelika Reil (Author)
Andreas Ruf (Author)
Sentot Santoso (Author)
Publication details: Blood, Vol.104(3), pp.727-734
Publisher: American Society of Hematology
Date published: 2004
DOI: 10.1182/blood-2003-11-3809
ISSN: 0006-4971
Organisation Unit: School of Health - Biomedicine; University of the Sunshine Coast, Queensland; School of Health and Sport Sciences - Legacy; School of Health and Behavioural Sciences - Legacy
Language: English
Record Identifier: 99449397102621
Output Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Web Of Science research areas: Hematology

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