The leukemoid reaction in Clostridium sordellii infection: neuraminidase induction of promyelocytic cell proliferation.
Life-threatening Clostridium sordellii infections have recently been reported in women undergoing therapeutic abortion, during natural childbirth, and in injection drug users. Shock, diffuse capillary leak, and a leukemoid reaction (LR) are cardinal features of these infections. The magnitude of the LR is highly correlated with mortality. We have isolated a 42-kDa extractable protein from C. sordellii culture supernatant that stimulates proliferation of promyelocytic HL-60 cells in vitro. Using mass spectrometry, we have identified this protein as the C. sordellii neuraminidase, NanS. Recombinant NanS (rNanS) dose dependently stimulated HL-60 cell proliferation. Increased proliferation was observed when HL-60 cells were cocultured with both rNanS and granulocyte-macrophage colony stimulating factor. In addition, NanS also modified vascular cell adhesion molecule 1, which orchestrates the release of mature and immature granulocytes from bone marrow stromal cells. Thus, neuraminidase likely plays an important role in the characteristic LR in C. sordellii infection.
Aldape
Michael John
MJ
Veterans Affairs Medical Center, Boise, ID 83702, and University of Idaho, USA. maldape32@hotmail.com
Bryant
Amy Evelyn
AE
Ma
Yongsheng
Y
Stevens
Dennis Leroy
DL
D000595:Amino Acid Sequence; D049109:Cell Proliferation / Q000187:drug effects; D003001:Cloning, Molecular; D003015:Clostridium Infections / Q000382:microbiology / Q000503:physiopathology*; D047989:Paraclostridium sordellii / Q000201:enzymology* / Q000235:genetics; D017931:DNA Primers / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D005098:Exotoxins / Q000494:pharmacology; D042381:Granulocyte Precursor Cells / Q000187:drug effects*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D007955:Leukemoid Reaction / Q000201:enzymology* / Q000276:immunology / Q000382:microbiology; D008969:Molecular Sequence Data; D009439:Neuraminidase / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors; D019010:Vascular Cell Adhesion Molecule-1 / Q000187:drug effects
D017931:DNA Primers; D005098:Exotoxins; D011994:Recombinant Proteins; D019010:Vascular Cell Adhesion Molecule-1; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D009439:Neuraminidase