Tuy nhiên, vai trò của PFO trong nguyên nhân bệnh vẫn không hoàn toàn rõ ràng, có thể là do thực tế là nó chỉ là một trong một số lượng rất lớn các yếu tố quyết định tính độc hại được biết đến hoặc tiềm năng sản xuất của C. perfringens. Các tính năng chính của sinh bệnh học của hoại tử khí C. perfringens qua trung gian là nghi ngờ gì nữa có thể giảng giải về C | 8 Mechanisms of Cell and Tissue Damage 235 and biophysical activity. However the role of PFO in disease causation is still not entirely clear probably due to the fact that it is only one of a very large number of known or potential virulence determinants produced by c. perfringens. The major features of the pathogenesis of c. per rmgens-mediated gas gangrene is unquestionably explicable in terms of c. perfringens a-toxin described above. Experimental evidence suggests that PFO plays only a minor role in the pathogenesis of gas gangrene by upregulating ICAM-1 see above for a-toxin thereby slightly contributing to the inhibition of PMN migration to the site of infection. Listeriolysin o LLO listeriolysin In contrast to the first two examples LLO is the most important virulence determinant of Listeria monocytogenes. We have already met listeriolysin in Ch. 4 it plays an important part in mediating the escape of L. monocytogenes from intraphagocytic vacuoles. Exogenous addition of LLO will like all other members of this group rapidly kill cells by rupturing the cytoplasmic membrane. However rupture of the phagocytic vacuole with release of organisms does not result in immediate death of the cell. This has been explained in terms of the initial acidification of the vacuole with concomitant activation of LLO the subsequent rise in pH deactivates LLO. LLO is also a potent trigger of host cell-signalling molecules. Many of the responses elicited by LLO are believed to be the result of the activation of cytosolic NF-kB hostcell stress-inducible transcription factor and its translocation into the nucleus where it acts as a transcriptional activator of different genes involved in the immune response. The pore-forming activity of LLO results in the release of antigens from the vacuole and stimulation of CD8 cytotoxic T cells which are known to afford protection against L. monocytogenes. This helps explain why patients recovering from L. monocytogenes infection have high levels
