Surgical stress impairment of murine natural killer cell cytotoxicity involves pre- and postbinding events.
NK cell cytotoxicity may provide an important first line of defense against the implantation of circulating tumor emboli. Previously we reported that murine hind limb amputation induces a rapid and marked impairment of perioperative NK cell cytotoxicity that is associated with increased metastatic activity compared to unmanipulated tumor-bearing controls. Because tumor emboli are systemically discharged in patients undergoing solid tumor resection, we thought it pertinent to begin examining the mechanism underlying the perioperative impairment of murine NK cell cytotoxicity. Studies presented in this report suggest that the mechanism of impairment is multifactorial and includes the surgical stress-induced expansion of splenic erythroblasts that successfully compete with NK cells for YAC-1 target binding sites. In addition, although there is no surgically mediated decrease in splenic NK cell content (as defined morphologically, phenotypically, and functionally), there is an acute decrease in maximal NK cell recycling capacity. An accurate understanding of the mechanisms mediating perioperative impairment of NK cell cytotoxicity may be important in the future development of NK-specific perioperative immunomodulation strategies.
Pollock
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RE
Department of General Surgery, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Lotzová
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E
Stanford
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SD
D000671:Amputation, Surgical / Q000009:adverse effects*; D000818:Animals; D001667:Binding, Competitive; D002448:Cell Adhesion / Q000187:drug effects; D002453:Cell Cycle; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004900:Erythroblasts / Q000276:immunology / Q000473:pathology; D005260:Female; D006411:Hematopoiesis, Extramedullary / Q000276:immunology; D006470:Hemorrhage / Q000209:etiology / Q000276:immunology; D006614:Hindlimb / Q000601:surgery; D007038:Hypotonic Solutions / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D008212:Lymphocyte Depletion; D051379:Mice; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013312:Stress, Physiological / Q000097:blood / Q000276:immunology*; D014407:Tumor Cells, Cultured
D007038:Hypotonic Solutions