Modulation of IgG and complement receptor expression of phagocytes in kidney cancer patients during treatment with interferon-alpha.
BACKGROUND
The mode of action of interferon involves both direct cytotoxic and antiproliferative effects on the tumour cell and indirect effects that facilitate immune detection by the host. Among the immunological effects of interferon-alpha is the activation of monocytes. As opsonin receptors are crucial in the function of phagocytes, e.g. monocytes and neutrophils, their modulation by interferon-alpha (INF-alpha) merit to be further clarified. We hypothesised that the role of phagocytes in defence against cancer is reflected in the expression of opsonin receptors for IgG and complement, which further could be modified by INF-alpha.


METHODS
The expression of the receptors for IgG and complement was studied in neutrophils and monocytes from blood samples of 18 kidney cancer patients treated with INF-alpha and from 39 healthy individuals. Blood samples were collected prior/to and during treatment with INF-alpha, 4.5 to 13.5 MU t.d.w., subcutaneously. After lysing the red blood cells, the samples were incubated with fluorochrome conjugated monoclonal antibodies specific for IgG (Fc gammaRI, -RII and -RIII) and complement (CR1, CR3) receptors and then analysed in flow cytometry. The results were given as the mean log fluorescence intensity (a measure of receptor number) and as the proportion of receptor-positive cells. In the in vitro experiments, the direct effect of interferon-alpha on the receptors of neutrophils and monocytes was studied.


RESULTS
In patients before any treatment, the expression of CR3 and Fc gammaRI receptors in neutrophils and all receptors except Fc gammaRIII in monocytes was significantly raised when compared to the controls. Treatment with INF-alpha, induced statistically significant; transient changes in CR1-receptor expression in neutrophils and Fc gammaRI expression in monocytes. Incubation of blood cells with INF-alpha in vitro confirmed the induction of CR1 receptors in neutrophils.


CONCLUSIONS
Changes in receptor expression reflect the inflammatory activation of phagocytes in metastatic kidney cancer. The pattern of receptor expression differs from that observed in infectious diseases. Interferon-alpha both in vivo and in vitro modulates the expression of phagocytic receptors.
Salminen
E
E
Department of Oncology and Radiotherapy, University of Turku, Finland.
Kankuri
M
M
Nuutila
J
J
Lilius
E M
EM
Pellimiemi
T T
TT
D000368:Aged; D000911:Antibodies, Monoclonal / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007128:Immunoglobulin Fragments / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism*; D016898:Interferon-alpha / Q000378:metabolism*; D007680:Kidney Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D010586:Phagocytes / Q000378:metabolism*; D010587:Phagocytosis; D011951:Receptors, Complement / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000097:blood; D013997:Time Factors
D000911:Antibodies, Monoclonal; D007128:Immunoglobulin Fragments; D007074:Immunoglobulin G; D016898:Interferon-alpha; D011951:Receptors, Complement; D011971:Receptors, Immunologic; C091196:opsonin receptor