Apoptosis and Bax, Bcl-2, Mcl-1 expression in neutrophils of Crohn's disease patients.
BACKGROUND
The etiology of Crohn's disease (CD) remains unknown, and the defective function of neutrophils appears to be associated with this pathology. Neutrophils undergo spontaneous apoptosis which, if not tightly regulated, can induce the development of chronic inflammatory disease. The Bcl-2 protein family is also involved in the regulation of neutrophil apoptosis.


METHODS
This study investigated the apoptosis and expression of some regulatory factors in CD patient and control polymorphonuclear neutrophils (PMN) in suspension and in adhesion on fibronectin, an extracellular matrix protein. These 2 conditions mimic circulating neutrophils before they are recruited at the intestinal levels, and their adhesion to tissue.


RESULTS
Apoptosis in CD patient PMN was delayed in suspension and accelerated in adhesion, which is the opposite of what happens in controls. Higher levels of Bax, Bcl-2, and Mcl-1 proteins were registered in freshly isolated CD patient PMN, in contrast to controls, in which Bcl-2 protein was undetectable. Among the studied pro- and antiapoptotic factors, Bax levels seem to be mainly related to the difference in apoptosis between PMN of CD patients and controls.


CONCLUSIONS
For the first time it has been demonstrated by direct experimental evidence that apoptosis in CD patient PMN is regulated differently from that of control PMN. Abnormal expression of regulating apoptosis proteins is shown in CD patient PMN. These data suggest that the defective functionality of neutrophils can be the early event responsible for the altered mucosal immune response in CD, and that neutrophil apoptosis may offer a new target for specific drugs and therapy tools.
Catarzi
Serena
S
Dipartimento di Scienze Biochimiche, Firenze, Italia.
Marcucci
Tommaso
T
Papucci
Laura
L
Favilli
Fabio
F
Donnini
Martino
M
Tonelli
Francesco
F
Vincenzini
Maria Teresa
MT
Iantomasi
Teresa
T
D000328:Adult; D017209:Apoptosis / Q000502:physiology*; D003424:Crohn Disease / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009504:Neutrophils / Q000737:chemistry* / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000097:blood*; D051028:bcl-2-Associated X Protein / Q000097:blood*
C481505:BCL2L15 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein