Loss of histochernical identity in mast cells lacking carboxypeptidase A

Loss of histochernical identity in mast cells lacking carboxypeptidase A

Autor Feyerabend, Thorsten B. Google Scholar
Hausser, Heinz Google Scholar
Tietz, Annette Google Scholar
Blum, Carmen Google Scholar
Hellman, Lars Google Scholar
Straus, Anita H. Autor UNIFESP Google Scholar
Takahashi, Helio K. Autor UNIFESP Google Scholar
Morgan, Ellen S. Google Scholar
Dvorak, Ann M. Google Scholar
Fehling, Hans Jorg Google Scholar
Rodewald, Hans Reimer Google Scholar
Instituição Univ Ulm
Uppsala Univ
Universidade Federal de São Paulo (UNIFESP)
Beth Israel Deaconess Med Ctr
Resumo 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, Me-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.
Idioma Inglês
Data 2005-07-01
Publicado em Molecular and Cellular Biology. Washington: Amer Soc Microbiology, v. 25, n. 14, p. 6199-6210, 2005.
ISSN 0270-7306 (Sherpa/Romeo, fator de impacto)
Editor Amer Soc Microbiology
Extensão 6199-6210
Fonte http://dx.doi.org/10.1128/MCB.25.14.6199-6210.2005
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000230267000033
URI http://repositorio.unifesp.br/handle/11600/28358

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