The murine antiapoptotic protein A1 is induced in inflammatory macrophages and constitutively expressed in neutrophils.
Myeloid leukocytes are thought to regulate their susceptibility to apoptosis 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 A1, an antiapoptotic Bcl-2 relative found in activated myeloid cells, during the course of an acute inflammatory response. Intraperitoneal infection of mice with the virulent RH strain of Toxoplasma gondii led to a 5- to 10-fold increase in A1 mRNA levels in peritoneal cells after several days. Bcl-2 expression was unchanged. The increase in A1 expression depended on the dose of the organism and coincided with a sharp increase in peritoneal cellularity. A1 protein levels were also increased as determined by Western blot analysis and immunohistochemical studies. All neutrophils and approximately half of the macrophages in the inflammatory exudate contained high levels of A1 in cytoplasm. A1 expression did not correlate with intracellular parasitization. Peripheral blood neutrophils from normal mice strongly expressed A1 protein, whereas normal monocytes showed only weak staining. Bax mRNA was induced in parallel with A1 in macrophages. Exudate macrophages and granulocytes that were apoptotic by TUNEL staining occasionally appeared to display A1 throughout the cell nucleus. These studies identify A1 as a potential regulator of apoptosis during acute inflammation.
Orlofsky
A
A
Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. orlofsky@aecom.yu.edu
Somogyi
R D
RD
Weiss
L M
LM
Prystowsky
M B
MB
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D005260:Female; D018398:Homeodomain Proteins; D007249:Inflammation / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D015778:Minor Histocompatibility Antigens; D009504:Neutrophils / Q000378:metabolism* / Q000473:pathology; D010529:Peritoneal Cavity / Q000469:parasitology / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D051818:Replication Protein C; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D013347:Subcellular Fractions / Q000276:immunology / Q000378:metabolism; D014122:Toxoplasma / Q000276:immunology; D014124:Toxoplasmosis, Animal / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051028:bcl-2-Associated X Protein
C096816:BCL2-related protein A1; C494827:Bax protein, mouse; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C096063:MATA1 protein, S cerevisiae; D015778:Minor Histocompatibility Antigens; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D051028:bcl-2-Associated X Protein; D051818:Replication Protein C