This could be caused by the lack of binding of aPC to EPCR, explaining its lack of effect on the NF-κB pathway, the inflammatory process, monocyte TF expression, and mortality.
The latter aspect, the need for higher pI C and CpG-A concentrations when stimulating WB vs. MC is consistent with our previously made observation of a lack of response of APC in WB at concentrations that maximally stimulate APC in MC [9], [10].
The lack of effect of APC on cytokine production and neutrophil influx that is prominent in H1N1 merits discussion.
We are concerned, however, that the current study does not yet go far enough in applying the methodology to discover new biology, that the experiments performed in macrophages are not yet conclusive, and that the imaging data need to be more quantitative and the (lack of) effects of APC treatment need to be documented more thoroughly.
The lack of signal from APC causes effector cells to differentiate, by default, into "transitory cells" that either die, or, in a small part, become long-lived memory cells.
The lack of effect on APC expression in our studies may be due to the short duration of our assays (hours – days) compared with the longer studies performed in the mouse models and in the clinic (weeks – 1 year).
The analysis of deviance indicated a significant lack-of-fit of the full APC model and significant non-linear effects for both birth cohort and calendar period.
This coupled with the rarity of β-catenin mutations (after early studies suggesting much higher rates (Sparks et al, 1998)) and the lack of mutual exclusivity with APC mutations has led to many discussions on the reasons for APC mutation in CRC.
For example, APC has potent anti-apoptotic effects on endothelial cells that remain even when modified forms of APC that lack anti-coagulant properties are used [ 2].
Truncations lacking the C-terminal domains of APC are the ones associated with tumorigenesis.
