The murine antiapoptotic protein A1 is induced in inflammatory macrophagesand constitutively expressed in neutrophils

Citation
A. Orlofsky et al., The murine antiapoptotic protein A1 is induced in inflammatory macrophagesand constitutively expressed in neutrophils, J IMMUNOL, 163(1), 1999, pp. 412-419
Citations number
63
Categorie Soggetti
Immunology
Journal title
JOURNAL OF IMMUNOLOGY
ISSN journal
00221767 → ACNP
Volume
163
Issue
1
Year of publication
1999
Pages
412 - 419
Database
ISI
SICI code
0022-1767(19990701)163:1<412:TMAPAI>2.0.ZU;2-B
Abstract
Myeloid leukocytes are thought to regulate their susceptibility to apoptosi s upon migration to a site of inflammation, However, factors that determine survival have not been well characterized in these cells. We have examined the expression of murine Al, an antiapoptotic Bcl-2 relative found in acti vated myeloid cells, during the course of an acute inflammatory response. I ntraperitoneal infection of mice with the virulent RH strain of Toxoplasma gondii led to a 5- to 10-fold increase in Al mRNA levels in peritoneal cell s after several days. Bcl-2 expression was unchanged, The increase in Al ex pression depended on the dose of the organism and coincided with a sharp in crease in peritoneal cellularity. Al protein levels were also increased as determined by Western blot analysis and immunohistochemical studies. All ne utrophils and approximately half of the macrophages in the inflammatory exu date contained high levels of Al in cytoplasm, Al expression did not correl ate with intracellular parasitization. Peripheral blood neutrophils from no rmal mice strongly expressed Al protein, whereas normal monocytes showed on ly weak staining, Pax mRNA was induced in parallel with Al in macrophages, Exudate macrophages and granulocytes that were apoptotic by TUNEL staining occasionally appeared to display Al throughout the cell nucleus. These stud ies identify Al as a potential regulator of apoptosis during acute inflamma tion.