title: Activation of human mast cells through stem cell factor receptor (KIT) is associated with expression of bcl-2.
abstract: BACKGROUND
  Mast cells (MCs) are multifunctional effector cells of the immune system. These cells originate from pluripotent hemopoietic progenitors. In contrast to basophils and other leukocytes, MCs exhibit a remarkably long life span (years) in vivo. Although a role for stem cell factor (SCF) and SCF receptor (KIT) in long-term survival of MCs has been proposed, the underlying biochemical mechanisms remain unknown.
  
  
  METHODS
  We have examined expression of 'survival-related' molecules of the bcl-2 family including bcl-2 and bcl-x(L), in primary human MCs and the human MC line HMC-1. Primary MCs were isolated from dispersed lung tissue by cell sorting using an antibody against KIT. mRNA expression was analyzed by RT-PCR and Northern blotting.
  
  
  RESULTS
  As assessed by RT-PCR, purified unstimulated lung MCs (>98% pure) exhibited KIT- and bcl-x(L) mRNA, but did not express bcl-2 mRNA. However, exposure of lung MCS to SCF (100 ng/ml) for 8 h resulted in expression of bcl-2 mRNA. Corresponding results were obtained by immunocytochemistry. In fact, exposure of MC to SCF resulted in expression of the bcl-2 protein whereas unstimulated MCs displayed only the bcl-x(L) protein without expressing the bcl-2 protein. The human MC leukemia cell line HMC-1, which contains a mutated and intrinsically activated SCF receptor, showed constitutive expression of both bcl-2 and bcl-x(L) at the mRNA and protein level.
  
  
  CONCLUSIONS
  Our data show that human MCs can express members of the bcl-2 family. It is hypothesized that bcl-x(L) plays a role in KIT-independent growth of MCs, whereas bcl-2 may be involved in KIT-dependent functions of MCs.
authors.affiliation: Department of Internal Medicine II, Division of Angiology, University of Vienna, Austria. Mehrdad.Baghestanian@univie.ac.at
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Baghestanian
authors.forename: John-Hendrik
authors.initials: JH
authors.lastname: Jordan
authors.forename: Hans P
authors.initials: HP
authors.lastname: Kiener
authors.forename: Dorian
authors.initials: D
authors.lastname: Bevec
authors.forename: Hermine
authors.initials: H
authors.lastname: Agis
authors.forename: Gerhard
authors.initials: G
authors.lastname: Fritsch
authors.forename: Michael R
authors.initials: MR
authors.lastname: Müller
authors.forename: Hans C
authors.initials: HC
authors.lastname: Bankl
authors.forename: Gerit-Holger
authors.initials: GH
authors.lastname: Schernthaner
authors.forename: Klaus
authors.initials: K
authors.lastname: Lechner
authors.forename: Peter
authors.initials: P
authors.lastname: Valent
mesh_terms: D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics*; D019009:Proto-Oncogene Proteins c-kit / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D011994:Recombinant Proteins; D019009:Proto-Oncogene Proteins c-kit