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Blood, 1 August 2004, Vol. 104, No. 3, pp. 727-734. Prepublished online as a Blood First Edition Paper on April 8, 2004; DOI 10.1182/blood-2003-11-3809. This Article Full Text (PDF) All Versions of this Article: 2003-11-3809v1 104/3/727    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sachs, U. J Articles by Santoso, S. Search for Related Content PubMed PubMed Citation Articles by Sachs, U. J Articles by Santoso, S. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 7, 2003 Accepted March 31, 2004 A human alloantibody (anti-Mart) interferes with Mac-1-dependent leukocyte adhesion Ulrich J Sachs, Triantafyllos Chavakis, Lin Fung, Alexander Lohrenz, Jurgen Bux, Angelika Reil, Andreas Ruf, and Sentot Santoso* Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany Department of Medicine I, University Hospital Heidelberg, Heidelberg, Germany Blood Service, Australian Red Cross, Brisbane, Australia Blood Service, Swiss Red Cross, Bern, Switzerland Center for Laboratory Medicine, Microbiology and Transfusion Medicine, Klinikum Karlsruhe, Karlsruhe, Germany * Corresponding author; email: sentot.santoso{at}immunologie.med.uni-giessen.de. The CD11b/CD18 integrin plays a crucial role in cell-cell adhesion processes. Recently, we described a case of severe neonatal alloimmune neutropenia (NAIN) due to an alloantibody against a variant of the CD11b subunit (Mart alloantigen). Allele-specific transfected cells allowed us to demonstrate that a 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 inhibits Mac-1-dependent adhesion of neutrophils and monocytic U937 cells to fibrinogen, intercellular adhesion molecule (ICAM)-1, pattern recognition receptor (RAGE), and glycoprotein Ib - but not to junctional adhesion molecule-C or UPAR. In line with this, anti-Mart blocked neutrophil and U937 cell adhesion to endothelial cells and the formation of platelet-leukocyte aggregates in whole blood under high shear. Other sera of anti-Mart from mothers who delivered 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 ability (1) to inhibit cell-cell adhesion, (2) to enhance the respiratory burst of neutrophils and (3) 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Han, X. Kim-Howard, H. Deshmukh, Y. Kamatani, P. Viswanathan, J. M. Guthridge, K. Thomas, K. M. Kaufman, J. Ojwang, A. Rojas-Villarraga, et al. Evaluation of imputation-based association in and around the integrin-{alpha}-M (ITGAM) gene and replication of robust association between a non-synonymous functional variant within ITGAM and systemic lupus erythematosus (SLE) Hum. Mol. Genet., March 15, 2009; 18(6): 1171 - 1180. [Abstract] [Full Text] [PDF] U. J. H. Sachs, K. Hattar, N. Weissmann, R. M. Bohle, T. Weiss, U. Sibelius, and J. Bux Antibody-induced neutrophil activation as a trigger for transfusion-related acute lung injury in an ex vivo rat lung model Blood, February 1, 2006; 107(3): 1217 - 1219. [Abstract] [Full Text] [PDF]

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