PMID- 26361072
OWN - NLM
STAT- MEDLINE
DCOM- 20160719
LR  - 20171116
IS  - 1537-2995 (Electronic)
IS  - 0041-1132 (Linking)
VI  - 55
IP  - 12
DP  - 2015 Dec
TI  - Human neutrophil antigen-3a antibodies induce neutrophil stiffening and 
      conformational activation of CD11b without shedding of L-selectin.
PG  - 2939-48
LID - 10.1111/trf.13299 [doi]
AB  - BACKGROUND: HNA-3a antibodies induce severe transfusion-related acute lung injury 
      (TRALI) in which neutrophils play a major role. As neutrophil passage through the 
      pulmonary microvasculature is a critical step in the pathogenesis of TRALI, we 
      investigated the impact of HNA-3a antibodies on two important factors that could 
      impair granulocyte passage through lung capillaries: the elasticity of 
      neutrophils and the expression and activation of adhesion molecules. STUDY DESIGN 
      AND METHODS: The impact of HNA-3a antibodies on the elasticity of neutrophils was 
      investigated using atomic force microscopy (AFM). Neutrophils were settled on 
      poly-2-hydroxyethyl-methacrylate-coated glass slides before treatment with 
      anti-HNA-3a plasma samples, control plasma, or control plasma containing 
      formyl-methionyl-leucyl-phenylalanine (fMLP). Elasticity measurements were 
      carried out in a temperature-controlled perfusion chamber using an atomic force 
      microscopy (AFM) device. The impact of HNA-3a antibodies on the surface 
      expression of total CD11b, activation of CD11b, and L-selectin (CD62L) shedding 
      was investigated by flow cytometry. The functional impact of HNA-3a antibodies on 
      neutrophil adhesion was assessed using fibrinogen-coated plates. RESULTS: HNA-3a 
      antibodies induced stiffening of neutrophils (+24%-40%; p < 0.05) to a similar 
      extent as fMLP. This effect was blocked by treatment of neutrophils with 
      cytochalasin D. While total surface expression of CD11b and L-selectin on 
      neutrophils was largely unaffected, HNA-3a antibodies induced 
      alloantigen-specific activation of CD11b (+72%-107%; p < 0.05) and increased 
      adhesion of neutrophils to fibrinogen. CONCLUSION: Accumulation of neutrophils in 
      the pulmonary microvasculature during severe TRALI is likely mediated by 
      increased rigidity and CD11b-mediated adhesion of neutrophils leading to 
      retention of neutrophils.
CI  - (c) 2015 AABB.
FAU - Berthold, Tom
AU  - Berthold T
AD  - Institute for Immunology and Transfusion Medicine, Universitatsmedizin 
      Greifswald, Greifswald, Germany.
FAU - Glaubitz, Michael
AU  - Glaubitz M
AD  - Nanostructure Group, ZIK HIKE-Center for Innovation Competence, Humoral Immune 
      Reactions in Cardiovascular Diseases, Ernst-Moritz-Arndt-University Greifswald, 
      Greifswald, Germany.
FAU - Muschter, Stefan
AU  - Muschter S
AD  - Institute for Immunology and Transfusion Medicine, Universitatsmedizin 
      Greifswald, Greifswald, Germany.
FAU - Gross, Stefan
AU  - Gross S
AD  - Department of Cardiology, Universitatsmedizin Greifswald, Greifswald, Germany.
AD  - DZHK-German Centre for Cardiovascular Research, Greifswald, Germany.
FAU - Palankar, Raghavendra
AU  - Palankar R
AD  - Nanostructure Group, ZIK HIKE-Center for Innovation Competence, Humoral Immune 
      Reactions in Cardiovascular Diseases, Ernst-Moritz-Arndt-University Greifswald, 
      Greifswald, Germany.
FAU - Reil, Angelika
AU  - Reil A
AD  - German Red Cross Blood Service West, Hagen, Germany.
FAU - Helm, Christiane A
AU  - Helm CA
AD  - Institute of Physics, Ernst-Moritz-Arndt-University Greifswald.
FAU - Bakchoul, Tamam
AU  - Bakchoul T
AD  - Institute for Immunology and Transfusion Medicine, Universitatsmedizin 
      Greifswald, Greifswald, Germany.
FAU - Schwertz, Hansjorg
AU  - Schwertz H
AD  - Institute for Immunology and Transfusion Medicine, Universitatsmedizin 
      Greifswald, Greifswald, Germany.
AD  - Lichtenberg-Professor for Experimental Hemostasis, Universitatsmedizin 
      Greifswald.
AD  - Program in Molecular Medicine, University of Utah, Salt Lake City, Utah.
AD  - Department of Surgery, University of Utah, Salt Lake City, Utah.
FAU - Bux, Jurgen
AU  - Bux J
AD  - Ruhr University Bochum, Bochum, Germany.
FAU - Greinacher, Andreas
AU  - Greinacher A
AD  - Institute for Immunology and Transfusion Medicine, Universitatsmedizin 
      Greifswald, Greifswald, Germany.
FAU - Delcea, Mihaela
AU  - Delcea M
AD  - Nanostructure Group, ZIK HIKE-Center for Innovation Competence, Humoral Immune 
      Reactions in Cardiovascular Diseases, Ernst-Moritz-Arndt-University Greifswald, 
      Greifswald, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150910
PL  - United States
TA  - Transfusion
JT  - Transfusion
JID - 0417360
RN  - 0 (CD11b Antigen)
RN  - 0 (HNA-3a antigen, human)
RN  - 0 (ITGAM protein, human)
RN  - 0 (Isoantibodies)
RN  - 0 (Isoantigens)
RN  - 126880-86-2 (L-Selectin)
SB  - IM
MH  - Acute Lung Injury/etiology
MH  - CD11b Antigen/chemistry/*physiology
MH  - Cell Adhesion
MH  - Humans
MH  - Isoantibodies/*physiology
MH  - Isoantigens/*immunology
MH  - L-Selectin/*physiology
MH  - Microscopy, Atomic Force
MH  - Neutrophils/*physiology
MH  - Protein Conformation
MH  - Transfusion Reaction
EDAT- 2015/09/12 06:00
MHDA- 2016/07/20 06:00
CRDT- 2015/09/12 06:00
PHST- 2015/02/09 00:00 [received]
PHST- 2015/05/27 00:00 [revised]
PHST- 2015/06/29 00:00 [accepted]
PHST- 2015/09/12 06:00 [entrez]
PHST- 2015/09/12 06:00 [pubmed]
PHST- 2016/07/20 06:00 [medline]
AID - 10.1111/trf.13299 [doi]
PST - ppublish
SO  - Transfusion. 2015 Dec;55(12):2939-48. doi: 10.1111/trf.13299. Epub 2015 Sep 10.