Proposed scheme for spontaneous apoptotic pathway in eosinophils and the inhibitory target of IL-5.

Spontaneous eosinophil apoptosis involves caspase-independent Bax translocation to the mitochondria, cytochrome crelease, and perturbation of the mitochondrial membrane followed by activation of caspase-9, -3, and -7, similar to the pathway of chemical-induced apoptosis. Caspase-3 activation of caspase-6 followed by activation of caspase-8 is proposed to form an amplification loop. IL-5 inhibits eosinophil apoptosis at an as yet undetermined site upstream of Bax translocation, cytochrome c release, and caspase activation. The IL-5 antiapoptotic signal is transduced by recruitment and activation of Jak2 and Lyn tyrosine kinases, and SHPTP-2 to the receptor, resulting in activation of Jak/STAT and Ras-Raf-MAPK pathways (see text for details). Dashed arrows represent protein translocation.