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Molecular and Cellular Biology, July 2005, p. 6199-6210, Vol. 25, No. 14
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.14.6199-6210.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Loss of Histochemical Identity in Mast Cells Lacking Carboxypeptidase A

Thorsten B. Feyerabend,1 Heinz Hausser,2 Annette Tietz,1 Carmen Blum,1 Lars Hellman,3 Anita H. Straus,4 Hélio K. Takahashi,4 Ellen S. Morgan,5 Ann M. Dvorak,5 Hans Jörg Fehling,1 and Hans-Reimer Rodewald1*

Department of Immunology,1 Department of Orthopedics, University of Ulm, D-89070 Ulm, Germany,2 Department of Cell and Molecular Biology, Biomedical Center, Uppsala University, S-751 24 Uppsala, Sweden,3 Department of Biochemistry, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo 04023-900, Brazil,4 Department of Pathology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, Massachusetts 022155

Received 7 December 2004/ Returned for modification 17 March 2005/ Accepted 21 April 2005

Mast cell carboxypeptidase A (Mc-cpa) is a highly conserved secretory granule protease. The onset of expression in mast cell progenitors and lineage specificity suggest an important role for Mc-cpa in mast cells. To address the function of Mc-cpa, we generated Mc-cpa-null mice. Mc-cpa–/– mast cells lacked carboxypeptidase activity, revealing that Mc-cpa is a nonredundant enzyme. While Mc-cpa–/– peritoneal mast cells were ultrastructurally normal and synthesized normal amounts of heparin, they displayed striking histochemical and biochemical hallmarks of immature mast cells. Wild-type peritoneal mast cells had a mature phenotype characterized by differential histochemical staining with proteoglycan-reactive dyes (cells do not stain with alcian blue but stain with safranin and with berberine) and a high side scatter to forward scatter ratio by flow cytometry and were detergent resistant. In contrast, Mc-cpa–/– peritoneal mast cells, like immature bone marrow-derived cultured mast cells, stained with alcian blue normally or weakly and either did not stain with safranin and berberine or stained weakly, had a low side scatter to forward scatter ratio, and were detergent sensitive. This phenotype was partially ameliorated with age. Thus, histochemistry and flow cytometry, commonly used to measure mast cell maturation, deviated from morphology in Mc-cpa–/– mice. The Mc-cpa–/– mast cell phenotype was not associated with defects in degranulation in vitro or passive cutaneous anaphylaxis in vivo. Collectively, Mc-cpa plays a crucial role for the generation of phenotypically mature mast cells.

* Corresponding author. Mailing address: Department of Immunology, University of Ulm, D-89070 Ulm, Germany. Phone: 49-731-5002 3360. Fax: 49-731-5002 3367. E-mail: hans-reimer.rodewald{at}uni-ulm.de.

Molecular and Cellular Biology, July 2005, p. 6199-6210, Vol. 25, No. 14
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.14.6199-6210.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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