The marginating-pulmonary immune compartment in rats: characteristics of continuous inflammation and activated NK cells.
A significant role has been indicated for cellular immunity in controlling circulating cancer cells, but most autologous tumor cells seem resistant, in vitro, to natural killer cell (NKC) and cytotoxic T lymphocytes cytotoxicity. Addressing this apparent contradiction, we recently identified a unique leukocyte population, marginating-pulmonary (MP)-leukocytes, which exhibit potent natural killer (NK) cytotoxicity. Here, we characterize the MP-compartment in naive and immunostimulated rats, and assessed its cytotoxicity against "NK-resistant" tumors cells. Animals were treated with poly I-C (3x0.2 mg/kg) or saline, and circulating-leukocytes and MP-leukocytes were collected and analyzed in terms of cellular composition, cellular activation markers, and NK cytotoxicity of leukocytes and purified NKCs. Compared with circulating-leukocytes, MP-leukocytes showed greater proportion of granulocytes, monocytes, NKCs, and large NKCs; higher expression of activation and adhesion markers (CD25, CD11a, CD11b, and NKR-P1, IFN-gamma); and elevated NK cytotoxicity of leukocytes and purified NKCs against several syngeneic and xenogeneic NK-resistant target cells (from both F344 and BDX inbred rats). In immunostimulated animals (treated with poly I-C), but not in naive animals, purified NKCs from the MP-compartment showed markedly superior cytotoxicity, suggesting that poly I-C immunostimulation uniquely affect MP-NKCs, and that in naive animals other MP-leukocytes support NK cytotoxicity. Overall, the results suggest that the MP-compartment is characterized by a continuous activated inflammatory microenvironment uniquely affected by immunostimulation. If similarly potent MP-NKCs exist in patients, then circulating autologous tumor cells that are considered "NK-resistant" could actually be controlled by MP-NKCs. Innate immunity may assume greater role in controlling malignant spread, especially after immunostimulation.
Melamed
Rivka
R
Department of Psychology, Neuroimmunology Research Unit, Tel Aviv University, Tel Aviv 69978, Ramit Aviv, Israel.
Rosenne
Ella
E
Benish
Marganit
M
Goldfarb
Yael
Y
Levi
Ben
B
Ben-Eliyahu
Shamgar
S
D000818:Animals; D002469:Cell Separation; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D005434:Flow Cytometry; D007249:Inflammation / Q000276:immunology*; D007369:Interferon Inducers / Q000276:immunology / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D008168:Lung / Q000166:cytology / Q000276:immunology*; D008297:Male; D009374:Neoplasms, Experimental / Q000276:immunology*; D010641:Phenotype; D011070:Poly I-C / Q000276:immunology / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344
D007369:Interferon Inducers; D011070:Poly I-C