Regulation of eosinophil and neutrophil apoptosis--similarities and differences.
Apoptosis is the most common form of physiologic cell death and a necessary process to maintain cell numbers in multicellular organisms. In many chronic inflammatory diseases, reduced cell death of different types of granulocytes is one important mechanism for cell accumulation. Granulocytes are constantly produced in large amounts in the bone marrow and the same numbers die, under normal circumstances, within a defined time period. Changing the rate of apoptosis rapidly changes cell numbers in such systems. Overexpression of IL-5 appears to be crucial for delaying eosinophil apoptosis in many allergic disorders, whereas overexpression of GM-CSF and G-CSF is associated with suppression of neutrophil apoptosis in bacterial and non-bacterial inflammations. Cytokine withdrawal leads to the induction of apoptosis both in vitro and in vivo. In contrast to the role of survival cytokines, little is known about the role of death factors and their receptors in the regulation of granulocyte apoptosis. Recent observations suggest a role for mitochondria in both eosinophil and neutrophil apoptosis, although the mechanisms that trigger mitochondria to release pro-apoptotic factors remain to be determined. Besides similarities, there are differences in the regulation of apoptosis between these granulocyte subtypes that include both expression and function of Bcl-2 and caspase family members. The identification of differences in the apoptosis regulation may help to define new molecular targets that allow specific induction of either eosinophil or neutrophil apoptosis by pharmacological means.
Simon
H U
HU
Department of Pharmacology, University of Bern, Switzerland. hus@pki.unibe.ch
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D020169:Caspases / Q000502:physiology; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000502:physiology; D004789:Enzyme Activation; D004804:Eosinophils / Q000166:cytology* / Q000187:drug effects; D053222:Fas Ligand Protein; D016179:Granulocyte Colony-Stimulating Factor / Q000502:physiology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology; D018398:Homeodomain Proteins; D006801:Humans; D015848:Interleukin-5 / Q000502:physiology; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D015778:Minor Histocompatibility Antigens; D008928:Mitochondria / Q000502:physiology; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D051818:Replication Protein C; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D019014:fas Receptor / Q000502:physiology
C096816:BCL2-related protein A1; C494811:BCL2L1 protein, human; C494812:Bcl2l1 protein, mouse; D015853:Cysteine Proteinase Inhibitors; D004268:DNA-Binding Proteins; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D018398:Homeodomain Proteins; D015848:Interleukin-5; C096063:MATA1 protein, S cerevisiae; D008562:Membrane Glycoproteins; D015778:Minor Histocompatibility Antigens; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D019014:fas Receptor; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D020169:Caspases; D051818:Replication Protein C