Differences in leucocyte-endothelium interactions between normal and adenocarcinoma bearing tissues in response to radiation.
Previously, we demonstrated that the interaction between leucocytes and endothelial cells in tumour tissues is greatly diminished compared with normal tissues under several induced inflammatory conditions. Radiation has been reported to cause release of inflammatory mediators and to promote neutrophil adhesions to cultured endothelial monolayers. In this study, we tested the hypothesis that radiation would cause increased leucocyte rolling and adhesion in both tumour and normal tissues. We examined these two parameters in response to 6 Gy of gamma-radiation in mammary adenocarcinomas implanted into rat skinfold window chambers as well as normal (i.e. non-tumour-bearing) preparations. Leucocyte rolling and adhesion were measured in terms of flux of rolling leucocytes (F(rolling)) and density of adhering leucocytes (D(adhering)) in microvessels. F(rolling) and D(adhering) were measured in two groups of preparations: irradiated and control. In normal preparations, F(rolling) and D(adhering) were both increased significantly by radiation. In contrast, in adenocarcinoma-bearing preparations, F(rolling) and D(adhering) were either unchanged (in the tumour centre) or reduced (in tumour periphery and the normal tissue surrounding the tumour) by radiation. Radiation did not cause changes in haemodynamics in these preparations, thus the observed changes in leucocyte rolling and adhesion could not be accounted for by haemodynamic factors. These results indicate that: (1) in normal preparations, radiation could cause inflammation as manifested by increased leucocyte rolling and adhesion; and (2) in tumour-bearing preparations, radiation caused changes in the vascular surface properties such that they became less adhesive to leucocytes. Such differences in radiation response may have important implications for radiation therapy and provide new insights into the unique features of tumours.
Wu
N Z
NZ
Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710.
Ross
B A
BA
Gulledge
C
C
Klitzman
B
B
Dodge
R
R
Dewhirst
M W
MW
D000230:Adenocarcinoma / Q000098:blood supply / Q000503:physiopathology*; D000818:Animals; D002448:Cell Adhesion / Q000528:radiation effects; D002465:Cell Movement / Q000528:radiation effects; D015194:Diffusion Chambers, Culture; D004730:Endothelium, Vascular / Q000528:radiation effects*; D007958:Leukocyte Count; D007962:Leukocytes / Q000528:radiation effects*; D015674:Mammary Neoplasms, Animal / Q000098:blood supply / Q000503:physiopathology*; D011829:Radiation Dosage; D051381:Rats; D011916:Rats, Inbred F344