Limits...
A novel IgM-H-ficolin complement pathway to attack allogenic cancer cells in vitro.

Lei X, Liu C, Azadzoi K, Li C, Lu F, Xiang A, Sun J, Guo Y, Zhao Q, Yan Z, Yang J - Sci Rep (2015)

Bottom Line: The pentameric serum IgMs are critical to immune defense and surveillance through cytotoxicity against microbes and nascent cancer cells.Ficolins, a group of oligomeric lectins with an overall structure similar to C1q and mannose-binding lectin (MBL) participate in microbe infection and apoptotic cell clearance by activating the complement lectin pathway or a primitive opsonophagocytosis.It remains unknown whether serum IgMs interplay with ficolins in cancer immunosurveillance.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Cancer Biology, Department of Pharmacogenomics, School of Pharmacy, the Fourth Military Medical University, Xi'an, 710032 China.

ABSTRACT
The pentameric serum IgMs are critical to immune defense and surveillance through cytotoxicity against microbes and nascent cancer cells. Ficolins, a group of oligomeric lectins with an overall structure similar to C1q and mannose-binding lectin (MBL) participate in microbe infection and apoptotic cell clearance by activating the complement lectin pathway or a primitive opsonophagocytosis. It remains unknown whether serum IgMs interplay with ficolins in cancer immunosurveillance. Here we report a natural cancer killing of different types of cancer cells by sera from a healthy human population mediated by a novel IgM-H-ficolin complement activation pathway. We demonstrate for the first time that H-ficolin bound to a subset of IgMs in positive human sera and IgM-H-ficolin deposited on cancer cells to activate complement attack in cancer cells. Our data suggest that the IgM-H-ficolin -mediated complement activation pathway may be another defensive strategy for human cancer immunosurveillance.

No MeSH data available.


Related in: MedlinePlus

H-ficolin was essential for the tumor cell lysing process.(a) The cytolysis of KATO III cells by PHS in the presence of the polyclonal antibody against human H- or L- ficolin. (b) Immunofluorescence images of deposition of ficolins on KATO III cells. (c) The H-ficolin-/albumin-depleted positive or negative sera (H/A-PHS or -NHS) and the purified H-ficolin-/albumin (H/A) were analyzed by C. Blue and Western Blotting. (d) The L-ficolin-depleted PHS (L-PHS) was analyzed by C. Blue and Western blotting. (e) The cell lysing activity of H-PHS and L-PHS in KATO III cells. (f) The cell lysing and binding activity of the purified H-ficolin (P-H/A) and H/A-PHS in KATO III cells. (NS indicates p > 0.05, *p < 0.05, **p < 0.01).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4296296&req=5

f3: H-ficolin was essential for the tumor cell lysing process.(a) The cytolysis of KATO III cells by PHS in the presence of the polyclonal antibody against human H- or L- ficolin. (b) Immunofluorescence images of deposition of ficolins on KATO III cells. (c) The H-ficolin-/albumin-depleted positive or negative sera (H/A-PHS or -NHS) and the purified H-ficolin-/albumin (H/A) were analyzed by C. Blue and Western Blotting. (d) The L-ficolin-depleted PHS (L-PHS) was analyzed by C. Blue and Western blotting. (e) The cell lysing activity of H-PHS and L-PHS in KATO III cells. (f) The cell lysing and binding activity of the purified H-ficolin (P-H/A) and H/A-PHS in KATO III cells. (NS indicates p > 0.05, *p < 0.05, **p < 0.01).

Mentions: To test whether ficolins are invloved in the cancer cell destruction activity, polyclonal antibodies against H- and L-ficolin were used to block complement activation. Both H- and L-ficolins inhibited lysis of KATO III cells in those matched PHS (Fig. 3a). To exclude the possible cross reaction between H- and L-ficolin with the polyclonal antibodies, deposition of H- and L-ficolin on the KATO III cell surface was examined by pre-incubation with heat-inactivated, matched PHS or NHS. The deposited ficolins on the cell surface were detected with monoclonal antibodies specific to H- or L-ficolin. Positive signals were detected only with the H-ficolin antibody; no signal was detected when the L-ficolin antibody was used (Fig. 3b). These results indicate that H-ficolin specifically deposited on KATO III cancer cell surface, but L-ficolin did not. Notably, no deposition was observed when heat-inactivated, compatible NHS were used. This suggested that only H-ficolin from the population whose sera were matched for “ABO” and positive for killing cancer cells could be deposited on the cancer surface, whereas H-ficolin from the population whose sera were matched for “ABO” and negative could not.


A novel IgM-H-ficolin complement pathway to attack allogenic cancer cells in vitro.

Lei X, Liu C, Azadzoi K, Li C, Lu F, Xiang A, Sun J, Guo Y, Zhao Q, Yan Z, Yang J - Sci Rep (2015)

H-ficolin was essential for the tumor cell lysing process.(a) The cytolysis of KATO III cells by PHS in the presence of the polyclonal antibody against human H- or L- ficolin. (b) Immunofluorescence images of deposition of ficolins on KATO III cells. (c) The H-ficolin-/albumin-depleted positive or negative sera (H/A-PHS or -NHS) and the purified H-ficolin-/albumin (H/A) were analyzed by C. Blue and Western Blotting. (d) The L-ficolin-depleted PHS (L-PHS) was analyzed by C. Blue and Western blotting. (e) The cell lysing activity of H-PHS and L-PHS in KATO III cells. (f) The cell lysing and binding activity of the purified H-ficolin (P-H/A) and H/A-PHS in KATO III cells. (NS indicates p > 0.05, *p < 0.05, **p < 0.01).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4296296&req=5

f3: H-ficolin was essential for the tumor cell lysing process.(a) The cytolysis of KATO III cells by PHS in the presence of the polyclonal antibody against human H- or L- ficolin. (b) Immunofluorescence images of deposition of ficolins on KATO III cells. (c) The H-ficolin-/albumin-depleted positive or negative sera (H/A-PHS or -NHS) and the purified H-ficolin-/albumin (H/A) were analyzed by C. Blue and Western Blotting. (d) The L-ficolin-depleted PHS (L-PHS) was analyzed by C. Blue and Western blotting. (e) The cell lysing activity of H-PHS and L-PHS in KATO III cells. (f) The cell lysing and binding activity of the purified H-ficolin (P-H/A) and H/A-PHS in KATO III cells. (NS indicates p > 0.05, *p < 0.05, **p < 0.01).
Mentions: To test whether ficolins are invloved in the cancer cell destruction activity, polyclonal antibodies against H- and L-ficolin were used to block complement activation. Both H- and L-ficolins inhibited lysis of KATO III cells in those matched PHS (Fig. 3a). To exclude the possible cross reaction between H- and L-ficolin with the polyclonal antibodies, deposition of H- and L-ficolin on the KATO III cell surface was examined by pre-incubation with heat-inactivated, matched PHS or NHS. The deposited ficolins on the cell surface were detected with monoclonal antibodies specific to H- or L-ficolin. Positive signals were detected only with the H-ficolin antibody; no signal was detected when the L-ficolin antibody was used (Fig. 3b). These results indicate that H-ficolin specifically deposited on KATO III cancer cell surface, but L-ficolin did not. Notably, no deposition was observed when heat-inactivated, compatible NHS were used. This suggested that only H-ficolin from the population whose sera were matched for “ABO” and positive for killing cancer cells could be deposited on the cancer surface, whereas H-ficolin from the population whose sera were matched for “ABO” and negative could not.

Bottom Line: The pentameric serum IgMs are critical to immune defense and surveillance through cytotoxicity against microbes and nascent cancer cells.Ficolins, a group of oligomeric lectins with an overall structure similar to C1q and mannose-binding lectin (MBL) participate in microbe infection and apoptotic cell clearance by activating the complement lectin pathway or a primitive opsonophagocytosis.It remains unknown whether serum IgMs interplay with ficolins in cancer immunosurveillance.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Cancer Biology, Department of Pharmacogenomics, School of Pharmacy, the Fourth Military Medical University, Xi'an, 710032 China.

ABSTRACT
The pentameric serum IgMs are critical to immune defense and surveillance through cytotoxicity against microbes and nascent cancer cells. Ficolins, a group of oligomeric lectins with an overall structure similar to C1q and mannose-binding lectin (MBL) participate in microbe infection and apoptotic cell clearance by activating the complement lectin pathway or a primitive opsonophagocytosis. It remains unknown whether serum IgMs interplay with ficolins in cancer immunosurveillance. Here we report a natural cancer killing of different types of cancer cells by sera from a healthy human population mediated by a novel IgM-H-ficolin complement activation pathway. We demonstrate for the first time that H-ficolin bound to a subset of IgMs in positive human sera and IgM-H-ficolin deposited on cancer cells to activate complement attack in cancer cells. Our data suggest that the IgM-H-ficolin -mediated complement activation pathway may be another defensive strategy for human cancer immunosurveillance.

No MeSH data available.


Related in: MedlinePlus