Degranulation and Intracellular Killing of Bacteria

Abstract

Metchnikoff knew that neutrophils possessed "ferments" capable of digesting gelatin and other proteins, and that phagocytosed grains of litmus sometimes turned red. He knew that organisms taken up by neutrophils were enclosed in vacuoles and not admitted to the cytoplasm proper, and that in the vacuoles they were slowly digested. He said: We are at present ignorant of the precise manner in which this digestive and other destructive action is accomplished, and do not even know whether the substance which kills the microbes is a ferment or not. In 1894, Kanthack and Hardy inserted bacteria contained in tubes or chambers into the peritoneal cavity of rabbits or under the skin. 1 Granular leukocytes accumulated, and the eosinophil granules were big enough to see clearly: The coarsely granular oxyphile cells were seen to apply themselves to a chain of bacilli, and to extend along it. The granules then travelled, usually in groups, to those portions of the cell in immediate contact with the bacilli, and there they were seen to diminish in size to mere points, and ultimately to disappear. The rate of loss of granular substance is very rapid. . . for an appreciable diminution may be observed in a quarter of an hour. Kanthack and Hardy knew that antibacterial substances could be extracted from lymph nodes, and suggested that leukocytes killed bacteria by dis-charging onto them analogous substances from their granules. 149 P. Murphy, The Neutrophil © Plenum Publishing Corporation 1976 150 Chapter 7 Here was a virtually complete description of bacterial killing in neutro-phils, but the observations were submitted to the great physiologist C. S. Sherrington, who could not confirm them, and they were forgotten. Other early workers attempted to explain bacterial killing by the low pH (-5) that was thought to exist in neutrophil cytoplasm. Alexander Fleming discovered a basic protein, lysozyme, which hydrolyzed the cell walls of some bacteria. However, most ofthe susceptible bacteria were nonpathogenic, and some organisms that the neutrophil was known to kill were resistant to lysozyme. Various substances from normal tissues were found to kill bacteria, but since they were released only following disrup-tion of cells, it seemed unlikely that they could be of physiological importance. 7.2. Phagocytin