Activation of human mast cells through stem cell factor receptor (KIT) is associated with expression of bcl-2.
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.
Baghestanian
Mehrdad
M
Department of Internal Medicine II, Division of Angiology, University of Vienna, Austria. Mehrdad.Baghestanian@univie.ac.at
Jordan
John-Hendrik
JH
Kiener
Hans P
HP
Bevec
Dorian
D
Agis
Hermine
H
Fritsch
Gerhard
G
Müller
Michael R
MR
Bankl
Hans C
HC
Schernthaner
Gerit-Holger
GH
Lechner
Klaus
K
Valent
Peter
P
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
D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D011994:Recombinant Proteins; D019009:Proto-Oncogene Proteins c-kit