"Toxic" neutrophils from humans with severe bacterial infections, identified by the presence of Döhle bodies, "toxic" granules, and vacuoles were shown to differ from normal neutrophils both in ultrastructure and in lysosome activity.
Döhle bodies were identified as lamellar aggregates of rough endoplasmic reticulum. Toxic granules corresponded to the azurophilic granules usually identified by Romanowsky stains only in neutrophil precursors. By electron microscopy such granules were large, electron-dense, and peroxidase positive; they could usually be distinguished from the smaller, less dense, "specific" granules also present in control neutrophils, but in the latter they became visible by light microscopy only after prolonged staining or following fixation with glutaraldehyde. These observations suggest that toxic granules represent an abnormal staining reaction of the large dense granules in the toxic cells, and not phagocytized material, newly formed abnormal granules or autophagic bodies.
Alkaline phosphatase activity was significantly greater in toxic neutrophils than in normal ones; 80% of the activity of both was located in the lysosome fraction. Beta glucuronidase was normal. Total acid phosphatase was normal, but the percentage located in the nonlysosome fraction of toxic neutrophils was increased, suggesting that lysosomes were "labilized."
Formation of neutral red vacuoles in supravitally stained preparations, an index of lysosome activity, occurred more rapidly in toxic neutrophils. This reaction paralleled degranulation and the formation of clear vacuoles in unstained wet mounts and could be blocked by colchicine, a lysosome stabilizer, or enhanced by procedures which activate lysosomes. "Autophagic" vacuoles were observed by electron microscopy in some toxic neutrophils.
These observations are discussed in relation to the concept that the "toxic" neutrophils in severe bacterial infection reflect cellular immaturity and/or stimulation or degeneration.
Histochemical study of the tartrate‐resistant acid phosphatase isoenzyme was made on frozen sections of surgical specimens from leukemic reticuloendotheliosis. The tumor cells of this disease were found to have strong tartrate‐resistant enzyme activity. Control studies on preparations of malignant lymphoma, other hematologic disorders, neoplasms of nonhematopoietic organs and normal tissues showed very little isoenzyme activity. Exceptions were found in specimens involved by Hodgkin's disease and in an adrenal of one patient with aldosteronism. It was proposed that the histochemical demonstration of the isoenzyme in the bone marrow, liver, or spleen can be used as a diagnostic criterion for leukemic reticuloendotheliosis, thus differentiating it from lymphosarcoma and reticulum cell sarcoma.
Reports of negative tartrate-resistant acid phosphatase reactions in a few cases of leukemic reticuloendotheliosis prompted the authors to re-evaluate the diagnostic specificity of this test. As a result, they modified the test by (1) incorporating a dual-control system for excluding a false-negative test due to technical errors, and (2) instituting an objective grading system for assuring consistent interpretation of the test on blood smears. When these modifications were applied to materials of patients suspected to have leukemic reticuloendotheliosis, there was an excellent, although not specific, correlation between the positive test and the diagnosis of leukemic reticuloendotheliosis. Tartrate-resistant acid phosphatase reactions were positive, intermediate, and negative for 76, 21, and 3% of 29 patients who had leukemic reticuloendotheliosis, whereas the figures were 3, 32, and 65%, respectively, for 37 patients who had chronic lymphocytic leukemia and other hematologic disorders.
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