ANTI-CHEMOTACTIC ACTIVITY OF CAPSULAR POLYSACCHARIDE OF CRYPTOCOCCUS-NEOFORMANS IN-VITRO

In this study, we demonstrated the anti-chemotactic activity of the ca psular polysaccharides (CPSs) isolated from each of the heavily (H)- a nd weakly (W)-encapsulated strains of Cryptococcus neoformans in vitro , The capacity for activation of the alternative complement pathway (A CP) of cells of the two C., neoformans strains in fresh human sera was comparable to that of zymosan (insoluble control), whereas the capaci ty for generation of the chemotactic factor (CF) of the cells of the t wo strains in fresh murine sera was markedly lower in the order H- < W -strain than that of zymosan, Conversely, the capacities for ACP activ ation and CF generation of the CPSs were extremely lower than those of lipopolysaccharide (LPS, soluble control), When zymosan-activated mur ine serum was incubated with CPS, both CPSs inhibited CF activity dose dependently, When zymosan-activated serum was incubated with heat-kil led cells of each strain of C., neoformans, H and W the CF activity of the treated sera decreased significantly, suggesting that CPS per se did not affect the neutrophils directly, but CPS absorbed CF, On the o ther hand, both CPSs were shown to possess the O-acetyl groups in thei r molecules by H-1-nuclear magnetic resonance spectroscopy, The de-O-a cetylation of both CPSs increased the capacity for ACP activation to a level similar to that of LPS, and the de-O-acetylated CPS of both str ains exhibited a lower ability to inhibit CF than did native CPS, Coll ectively, these results suggest that the anti-chemotactic activity of CPS accounts for its ability to absorb the CF which was mostly generat ed at the sites around the cell wall of whole cells via the ACP, thus suppressing the inflammatory response by preventing dispersal of CF to the extracellular space; and also that the O-acetyl group is partly, if any, involved in the mechanism for incompetence in ACP activation a s well as the inhibition of CF.