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
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.