Excessive vulnerability of herpes-infected endothelium to lymphokine-activated lymphocytes: a possible role in lethal viral pneumonitis following bone marrow transplantation.
1. Lymphokine-activated killer cells are cytotoxic to human umbilical vein endothelial cells in vitro. 2. Cytotoxic efficiency of LAK cells correlates with serine esterase activity. 3. LAK cells generated from bone marrow transplant patients, as compared to normal volunteers, are significantly more cytotoxic for cultured endothelium, which correlates with their elevated serine esterase content and phenotypic NK-cell proportion. 4. Endothelium infected with herpes simplex virus for very brief periods (4 hr) becomes even more vulnerable to LAK cell-mediated injury. 5. Thus, bone marrow transplant patients harbor "primed" lymphocytes, highly liable to become lymphokine-activated killer cells. These cells have an NK phenotype, readily generate cytotoxic serine esterase activity, and manifest a proclivity to damage vascular endothelium--especially virally infected endothelium. We suggest this proclivity may underlie the severe endotheliitis and lethal pulmonary hemorrhage suffered by bone marrow transplant patients infected with herpesviruses.
Vercellotti
G M
GM
Department of Medicine, University of Minnesota 55455.
Kotasek
D
D
Jacob
H S
HS
D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D004730:Endothelium, Vascular / Q000276:immunology* / Q000382:microbiology; D006561:Herpes Simplex; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D011024:Pneumonia, Viral / Q000209:etiology*; D018139:Simplexvirus / Q000276:immunology*
D007376:Interleukin-2