Polymorphonuclear Leukocyte Lysosome Activities and Lymphocyte Transformation in Multiple Sclerosis and some other Central Nervous System Chronic Diseases

Abstract

The role of PMNL lysosomes was studied in some lesions of the central nervous system with special regard to multiple sclerosis patients. The significant decrease of acid hydrolases was observed in multiple sclerosis (MS) peripheral blood PMNL lysosomal granula and, in parallel, the increase of lysosome proteins mitogenic potency. The other lesions of the central nervous system such as apoplexy, brain tumors, brain trauma and epilepsy have not shown the MS-like activities of PMNLs. The role of PMNLs in pathogenesis of MS and in the stimulation of immunocompetent cells is suggested.

Extent and distribution of linkage disequilibrium around the SLC11A1 locus

“…Neutrophils are also known to play a potential role in the pathogenesis of RA because of their derived products being implicated in tissue damage, and also a role in the pathogenesis of MS and IBD. [68][69][70] In other words, IL8RA and IL8RB affect the functions of neutrophils and might play a role in these diseases. Thus, on the basis of biological functions, the genes encoding these receptors are potential candidate genes for these diseases.…”

Degradation of myelin basic protein by cerebrospinal fluid: Preservation of antigenic determinants under physiological conditions

“…The presence of neutral proteinases in CSF makes it highly likely that radioimmunoassays [ll-13, 22 46,48,49], the present studies indicate that once BP is in the CSF, it will be broken down into peptide fragments. The antigenic determinants of many of these fragments remain sufficiently intact to combine with anti-BP antibodies, some peptide fragments still capable of forming immunoprecipitates (Fig 7), but some, unable to form precipitates, still capable of combining with anti-BP antibodies, thereby inhibiting the formation of precipitates with whole BP or its larger fragments (see Fig 8).…”

“…Such demonstrations were also predictable from our earlier work showing immunoprecipitations with quite similar peptide fragments of BP [31. Do such observations afford any advance in our understanding of the pathogenesis of MS? If it could be determined why BP, BP fragments, or both occur in the CSF so selectively in MS [ l l , 22, [8,14,15,41,49] or present in serum [28] and acting at the neutral p H of extracellular fluids, other bonds would probably be broken, thereby releasing peptides which might be similar to those produced by the neutral proteinases present in CSF, as also demonstrated in Figures 4 and 5. A determination of the presence or absence of Nand C-terminal Phes in a significant number of the BP fragments in CSF from MS patients could throw light on whether the initial process in MS is related to cells or humoral factors, a critically important point in our understanding of the disease. Even if the catheptic peptides resulting from intracellular digestion were subsequently degraded by the neutral proteinases normally present in CSF and acting on the peptides only as CSF circulates from MS plaques through the ventriculospinal pathways, N -and Cterminal Phes would be preserved in a relatively high proportion of the smaller peptides unless aminopeptidases, carboxypeptidases, or both were also present.…”

Proteinases in inflammatory demyelinating disease

“…Some of the proteins existing in CSF and currently poorly [28] --, L T Goto et al [36] o ~" © o Govindaraian et al [37] o © --Guarnieri et al [38] ---T Riekkinen et al [75] o -+ -Tchorzewski et al [94] --J, $ a Symbols: -, not done; ~, increased; o, no change; $, decreased understood could be either proteinases, their precursors, or inhibitors and a further delineation of these may be important in understanding the proteolytic activities in CSF and, indirectly, the proteolytic activity within the CNS. In particular, the CSF of patients with infectious disease of the CNS has increased proteolytic enzymes.…”