Characterization of formylpeptide chemoattractant binding on neutrophils and monocytes from patients with head and neck cancer.
Monocytes from patients with head and neck tumors display a marked chemotactic deficiency in response to formylpeptide chemoattractants. Normal leukocytes possess receptors known to bind to chemotactic formylpeptides such as the hexapeptide N-formyl-nor-leucyl-leucyl-phenylalanyl-nor-leucyl-tyrosyl-lysine, with high specificity and great avidity. Light microscopic autoradiography was used to visualize the binding and subsequent cellular processing of the formylhexapeptide N-formyl-nor-leucyl-leucyl-phenylalanyl-nor-leucyl-[125I]tyrosyl-lysine to polymorphonuclear leukocytes (PMN) and monocytes from patients with epidermoid tumors of the head and neck. Surface-adherent leukocytes were exposed to 5 nM 125I-labeled hexapeptide for 15 minutes at 4 degrees C and were either fixed immediately or rinsed and then further incubated for 20 minutes at 37 degrees C prior to fixation. Cells underwent autoradiography, and silver grains associated with 400 cells were counted. There were no significant differences between the numbers of formylpeptide receptors on control and cancer patient PMN. However, there were significantly larger numbers of formylpeptide receptors (P less than .02) on cancer patient monocytes than on control monocytes. Cells that were allowed to process bound hexapeptide at 37 degrees C prior to fixation showed large decreases in the number of cell-associated silver grains. However, the amount of hexapeptide associated with PMN and monocytes treated in this way was the same for both control and tumor patients. In addition, histograms were plotted showing the amount of hexapeptide bound versus the frequency of cells at each level of binding. Examination of these histograms revealed that two major peaks or subpopulations occurred in each for neutrophils and monocytes from control patients. Histograms of grain counts for neutrophils and monocytes from tumor patients did not display two separate peaks of formylhexapeptide binding; instead, only one broad peak was evident. These observations indicated that: Tumor patient PMN expressed as many formylpeptide receptors as did control PMN, and tumor patient monocytes possessed significantly more receptors than did control monocytes. The disposition of formylpeptide initially bound to control and tumor patient leukocytes appeared to be essentially the same. Subpopulations existed in each control neutrophil and monocyte sample, one exhibiting approximately 30% more formylpeptide binding than the other. However, in the leukocytes obtained from tumor patients, the distinction between these two subpopulations had become obscured such that only one cell population was evident.
Walter
R J
RJ
Danielson
J R
JR
D002294:Carcinoma, Squamous Cell / Q000276:immunology*; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D006258:Head and Neck Neoplasms / Q000276:immunology*; D006801:Humans; D009000:Monocytes / Q000145:classification / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D009842:Oligopeptides / Q000378:metabolism / Q000494:pharmacology*; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000378:metabolism
D009842:Oligopeptides; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; C021642:F-chemotactic peptide