Lipoteichoic acid derived from Enterococcus faecalis modulates the functional characteristics of both normal peripheral blood leukocytes and native human acute myelogenous leukemia blasts.
OBJECTIVE
Several case reports have described complete hematological remissions for patients with otherwise untreated acute myelogenous leukemia (AML) who receive hematopoietic growth factor therapy during complicating bacterial infections. This may be caused by indirect cytokine effects, but direct effects of infecting agents on the malignant cells are also possible because bacterial molecules can bind to specific receptors expressed by normal and malignant leukocytes. Lipoteichoic acid (LTA) is a cell wall component of gram-positive bacteria, and it can activate normal immunocompetent cells through binding to specific cell membrane receptors.


METHODS
We investigated effects of LTA derived from Enterococcus faecalis on in vitro cultured (i) normal peripheral blood mononuclear cells (PBMC); (ii) remaining T cells derived from patients with hematologic malignancies and chemotherapy-induced leukopenia; and (iii) native human AML cells.


RESULTS
Increased interleukin 1beta (IL1beta) and IL8 release by in vitro cultured normal PBMC was observed after stimulation with LTA at concentrations > or =5 microg/mL; these levels were lower than for lipopolysaccharide (LPS)-stimulated cells and LTA antagonized LPS-induced cytokine release by normal PBMC. In most cases LTA did not alter T-cell proliferation for patients with chemotherapy-induced leukopenia. The LTA effects on AML blasts were investigated for 62 consecutive patients. LTA altered either cytokine (granulocyte-macrophage colony-stimulating factor + stem cell factor + IL3)-dependent proliferation or the release of IL1beta/IL8 for 23 patients; the effects were divergent but increased proliferation/cytokine levels were most commonly observed.


CONCLUSIONS
The LTA derived from E. faecalis can modulate the functional characteristics of normal leukocytes and native human AML blasts.
Division of Hematology, Haukeland University Hospital and The University of Bergen, Bergen, Norway. oystein.bruserud@haukeland.no
Øystein
Ø
Bruserud
Øystein
Ø
Wendelbo
Kristin
K
Paulsen
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D013293:Enterococcus faecalis / Q000737:chemistry*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D042381:Granulocyte Precursor Cells / Q000187:drug effects* / Q000502:physiology; D019337:Hematologic Neoplasms / Q000097:blood; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000097:blood*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000502:physiology; D007970:Leukopenia / Q000097:blood / Q000139:chemically induced; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology; D013682:Teichoic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D007375:Interleukin-1; D016209:Interleukin-8; D008070:Lipopolysaccharides; D013682:Teichoic Acids; D016179:Granulocyte Colony-Stimulating Factor; C009900:lipoteichoic acid