Human alloantibody anti-Mart interferes with Mac-1-dependent leukocyte adhesion.
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 Ibalpha 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.
Sachs
Ulrich J H
UJ
Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany.
Chavakis
Triantafyllos
T
Fung
Lin
L
Lohrenz
Alexander
A
Bux
Jürgen
J
Reil
Angelika
A
Ruf
Andreas
A
Santoso
Sentot
S
D000818:Animals; D001483:Base Sequence; D001792:Blood Platelets / Q000502:physiology; D018821:CD18 Antigens / Q000276:immunology*; D019556:COS Cells; D002448:Cell Adhesion / Q000276:immunology*; D002522:Chlorocebus aethiops; D017931:DNA Primers; D005434:Flow Cytometry; D005787:Gene Frequency; D005838:Genotype; D017127:Glycation End Products, Advanced / Q000502:physiology; D006098:Granulocytes; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D007518:Isoantibodies / Q000276:immunology*; D007519:Isoantigens / Q000276:immunology*; D016177:Macrophage-1 Antigen / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology*; D016133:Polymerase Chain Reaction; D014162:Transfection; D020298:U937 Cells
D018821:CD18 Antigens; D017931:DNA Primers; D017127:Glycation End Products, Advanced; C531098:HNA-4A antigen; D007518:Isoantibodies; D007519:Isoantigens; D016177:Macrophage-1 Antigen; D018799:Intercellular Adhesion Molecule-1