Influence of irradiation on neutrophilic granulocyte function

Abstract

BACKGROUND. Neoadjuvant radiotherapy is a common treatment modality for patients with Stage II and III rectal carcinoma but, after surgery, often is complicated by local infections. To define a possible influence of radiotherapy on neutrophilic granulocytes in the neighborhood of tumor cells, the authors investigated their function in vitro. METHODS. Density gradient-purified granulocytes from healthy donors were used for all tests. These cells were cocultured with the colon carcinoma cell line HRT-18 and irradiated. Their function was assessed by measuring luminol-enhanced chemiluminescence and migration against the chemoattractant formyl-methionylleucine-phenylalanine. RESULTS. Although irradiation decreased, the addition of tumor cells increased reactive-oxygen species release in granulocytes, which was enhanced further by phorbol myristate acid (PMA), even after several hours. All contacts with tumor cells, however, caused immediate radical release that was inversely proportional to the radiation dose. Naïve and irradiated cells were stimulated further by PMA. Migration of granulocytes clearly was inhibited by tumor cells and irradiation, whereas the depth of invasion was enhanced by higher doses of radiation. CONCLUSIONS. The current data show clearly that the influence of radiotherapy on local defense against colorectal carcinoma is limited and cannot explain the increased rate of infectious complications. © 2001 American Cancer Society.