PubMed Health⌕ Search

Biomedical subjects

S J Ackerman

Publications and source records attributed to S J Ackerman.

119 records · Page 7Linked to original sources
PubMed1982

Formation of Charcot-Leyden crystals by human basophils.

Charcot-Leyden crystals (CLC) are currently believed to be unique to the eosinophil and a hallmark of active eosinophilic inflammation or proliferation. The distinctiveness of the CLC to the eosinophil was questioned in 1965 by Archer and Blackwood (9), but their demonstration of CLC formation in basophils was ignored and later dismissed (1) as being the result of eosinophil contamination of basophil-enriched cell suspensions. We reexamined this question and showed that basophils obtained from the peripheral blood of normal individuals form CLC and that basophils contain a protein that is immunochemically indistinguishable from eosinophil CLC protein. These conclusions are based upon the findings that (a) crystal formation in basophils was demonstrated by specific histochemical staining of crystal-containing cells in highly enriched basophil suspensions prepared by fluorescence-activated cell sorter (FACS) purification of surface IgE-positive cells, (b) that enrichment for surface IgE-positive cells (primarily basophils) by the FACS also enriched for cells staining positively by immunofluorescence for eosinophil CLC protein, and (c) that CLC protein was measured by radioimmunoassay in cell extracts prepared from purified basophil suspensions containing 97-99% basophils and absolutely no contaminating eosinophils. These basophil extracts contained a protein immunochemically indistinguishable from eosinophil CLC protein. Based upon these findings, the CLC or the protein comprising the crystal (lysophospholipase) can no longer be considered as distinctive to the eosinophil. We must now consider the possibility that the presence of CLC in tissues, sputum, or stool may also represent basophil involvement in disease processes.

Animals↗
PubMed1982

Inhibition of antibody-dependent eosinophil-mediated cytotoxicity by heparin.

Killing of bloodstream forms of Trypanosoma cruzi, the unicellular parasite that causes Chagas' disease in humans, by human eosinophils in the presence of specific antibody to the parasite was inhibited by the polyanion heparin in a dose-dependent manner. The concentration of heparin required to completely abolish eosinophil-effected killing of the flagellate increased as the eosinophil to parasite ratio increased. These results suggest that antibody-dependent eosinophil-mediated cytotoxicity is mediated by basic constituents of the eosinophil granule.

Antibody Specificity↗
PubMed1981

Eosinophil granule major basic protein and Charcot-Leyden crystal protein in human tears.

We measured the levels of major basic protein and Charcot-Leyden crystal protein in tears from patients with ventral keratoconjunctivitis or miscellaneous inflammatory or noninflammatory ocular conditions, and from normal subjects. Patients with vernal keratoconjunctivitis had significantly increased levels of both proteins in their tears compared with the other subjects tested; levels of major basic protein seemed to correlate with the severity of the disease. The levels of Charcot-Leyden crystal protein paralleled those of major basic proteins.

Eosinophils↗
PubMed1981

Purification of human eosinophil-derived neurotoxin.

Human and animal eosinophils contain a powerful neurotoxin that causes selective neuronal and axonal damage to white matter of cerebellum and spinal cord of experimental animals when injected intrathecally. This reaction is termed the "Gordon phenomenon." We purified the eosinophil-derived neurotoxin from eosinophil-rich leukocyte suspensions or eosinophil granules from four patients with various hypereosinophilic syndromes. A single protein with an average molecular weight of 18,400 was isolated by sequential chromatography on Sephadex G-50 columns and analyzed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis of column fractions. The purified eosinophil-derived neurotoxin from the cells of these patients retained the potent neurotoxic activity of the crude eosinophil or eosinophil granule extracts in experimental animals. These animals developed the syndrome of stiffness and ataxia progressing to severe paralysis characteristic of the Gordon phenomenon. Histologic examination of the brains of animals injected with purified eosinophil-derived neurotoxin confirmed the characteristic widespread loss of Purkinje cells and severe spongiform vacuolation in the white matter of cerebellum, brain stem, and spinal cord. We have established the location of eosinophil-derived neurotoxin in the eosinophil granule and have shown that it is distinct from several other eosinophil proteins, the granule major basic protein, and the Charcot-Leyden crystal protein (lysophospholipase).

Animals↗
PubMed1981

Destruction of bloodstream forms of Trypanosoma cruzi by eosinophil granule major basic protein.

Human eosinophils are known to engage in an antibody-dependent cell-mediated cytotoxicity reaction causing destruction of virulent bloodstream forms of Trypanosoma cruzi. A similar cytotoxic effect was found in this work to be produced by the major basic proteins (MBP) purified from human and guinea pig eosinophil granules. Killing of T. cruzi by these proteins was concentration-dependent, with significant cytotoxicity observed at concentrations as low as 1 x 10(-5) M. Basicity appeared to be an important, but not the only, property required for the MBP molecule to destroy T. cruzi, since highly basic proteins such as arginine-rich histone and cytochrome C were inactive under the same conditions. However, other basic proteins, poly-L-arginine and protamine, lacked cytotoxicity at concentrations which were effective for MBP (1 x 10(-5) M), but killed the flagellates at higher concentrations (5 x 10(-5) M). Furthermore, heparin, an anionic molecule, effectively inhibited the cytotoxic effect of both human and guinea pig MBP on T. cruzi. Heating MBP at 56 degrees C for 4 hours, a treatment which causes the loss of reactivity of MBP with specific antibodies, effectively inhibited the lytic effect on the parasites. In contrast, heating had no effect on the cytotoxic effects of protamine or poly-L-arginine. Specific antiserum to MBP caused a marked reduction in the extent of trypanosome killing by MBP when added to reaction mixtures. The present results suggest that eosinophil-mediated killing of T. cruzi may be due to the discharge of basic granule components by the effector cells which are directly toxic for the parasite.

Animals↗