Esterase, Peptidase and Proteinase Activities of Human Cerebrospinal Fluid in Multiple Sclerosis

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

“…Cuzner et a1 [ 14,401 reported "basically the same" [40] or "directly proportional" [14] results with hemoglobin and BP at pH 7.6, but the actual values reported in their [14] shows that hemoglobin was digested at p H 3.6, albeit only 5 to 10% as much as at p H 7.6. Finally, whereas the ranges of our neutral and acid proteinase activities are approximately equal with BP as substrate (see Fig 1, Table 2 ) , the ranges reported by Rinne and Riekkinen [43] appear at least slightly different when hemoglobin was used as a substrate, with higher acid proteinase activities.…”

“…Of the several studies of proteolytic enzymes in CSF [14, 16,38,40,42,43], one [42] concerns only CSF pooled from normal volunteers, and another [38] considers only acid proteinase inhibitors; neither provides data which can be compared with the present results. Rinne and Riekkinen [43] reported acid and neutral proteinase activities using hemoglobin as substrate, and Cuzner et a1 114,16,401 presented only acid proteinase activities using BP as substrate.…”

“…Rinne and Riekkinen [43] reported acid and neutral proteinase activities using hemoglobin as substrate, and Cuzner et a1 114,16,401 presented only acid proteinase activities using BP as substrate. It is not clear just how comparable the results with the two substrates are.…”

“…Although statistically significant differences in the means of results obtained with CSF from patients with acute MS have been reported, especially for neutral proteinase [43], the biological and differential diagnostic significances are obscured by the great overlap in individual results, especially for acid proteinase [ 14, 401. The range of acid proteinase activities reported by Richards and Cuzner [40], upon which the summary of Cuzner et a1 [14] is based, is quite similar to the range of our results shown in Figure 1 and Table 2: 0 to 100 pg of BP degraded per hour per milliliter of CSF, with one value of 245 [40], as compared to 3.8 to 19.4%, or 38 to 194 pg of BP per hour per milliliter. Just how long Richards and Cuzner [40] kept their CSF samples frozen at -70°C is not stated, but we have noted that enzyme activities decrease after one week of such storage and have made a point of assaying all samples within this period.…”

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

“…Cuzner et a1 [ 14,401 reported "basically the same" [40] or "directly proportional" [14] results with hemoglobin and BP at pH 7.6, but the actual values reported in their [14] shows that hemoglobin was digested at p H 3.6, albeit only 5 to 10% as much as at p H 7.6. Finally, whereas the ranges of our neutral and acid proteinase activities are approximately equal with BP as substrate (see Fig 1, Table 2 ) , the ranges reported by Rinne and Riekkinen [43] appear at least slightly different when hemoglobin was used as a substrate, with higher acid proteinase activities.…”

“…Of the several studies of proteolytic enzymes in CSF [14, 16,38,40,42,43], one [42] concerns only CSF pooled from normal volunteers, and another [38] considers only acid proteinase inhibitors; neither provides data which can be compared with the present results. Rinne and Riekkinen [43] reported acid and neutral proteinase activities using hemoglobin as substrate, and Cuzner et a1 114,16,401 presented only acid proteinase activities using BP as substrate.…”

“…Rinne and Riekkinen [43] reported acid and neutral proteinase activities using hemoglobin as substrate, and Cuzner et a1 114,16,401 presented only acid proteinase activities using BP as substrate. It is not clear just how comparable the results with the two substrates are.…”

“…Although statistically significant differences in the means of results obtained with CSF from patients with acute MS have been reported, especially for neutral proteinase [43], the biological and differential diagnostic significances are obscured by the great overlap in individual results, especially for acid proteinase [ 14, 401. The range of acid proteinase activities reported by Richards and Cuzner [40], upon which the summary of Cuzner et a1 [14] is based, is quite similar to the range of our results shown in Figure 1 and Table 2: 0 to 100 pg of BP degraded per hour per milliliter of CSF, with one value of 245 [40], as compared to 3.8 to 19.4%, or 38 to 194 pg of BP per hour per milliliter. Just how long Richards and Cuzner [40] kept their CSF samples frozen at -70°C is not stated, but we have noted that enzyme activities decrease after one week of such storage and have made a point of assaying all samples within this period.…”

Schwann cell plasminogen activator is regulated by neurons

“…Elevated levels of proteolytic enzymes have been observed in and around demyelinating plaques (Einstein et al, 1972;Govindarajan et al, 1974;Rauch et al, 1973) as well as in cerebrospinal fluid in multiple sclerosis. Although such increases have been attributed to lymphocytes and macrophages Rinne and Rikkinen, 1968;Sibley et al, 1978), astrocytes also produce and secrete plasminogen activator (Toshniwal et al, 1987) suggesting that glial cells also participate in demyelination. Additionally, neutral proteinases including plasminogen activator (Brosnan et al, 1980a) degrade myelin basic protein and cause demyelination in vivo.…”

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

“…Cuzner et a1 [ 14,401 reported "basically the same" [40] or "directly proportional" [14] results with hemoglobin and BP at pH 7.6, but the actual values reported in their [14] shows that hemoglobin was digested at p H 3.6, albeit only 5 to 10% as much as at p H 7.6. Finally, whereas the ranges of our neutral and acid proteinase activities are approximately equal with BP as substrate (see Fig 1, Table 2 ) , the ranges reported by Rinne and Riekkinen [43] appear at least slightly different when hemoglobin was used as a substrate, with higher acid proteinase activities.…”

“…Of the several studies of proteolytic enzymes in CSF [14, 16,38,40,42,43], one [42] concerns only CSF pooled from normal volunteers, and another [38] considers only acid proteinase inhibitors; neither provides data which can be compared with the present results. Rinne and Riekkinen [43] reported acid and neutral proteinase activities using hemoglobin as substrate, and Cuzner et a1 114,16,401 presented only acid proteinase activities using BP as substrate.…”

“…Rinne and Riekkinen [43] reported acid and neutral proteinase activities using hemoglobin as substrate, and Cuzner et a1 114,16,401 presented only acid proteinase activities using BP as substrate. It is not clear just how comparable the results with the two substrates are.…”

“…Although statistically significant differences in the means of results obtained with CSF from patients with acute MS have been reported, especially for neutral proteinase [43], the biological and differential diagnostic significances are obscured by the great overlap in individual results, especially for acid proteinase [ 14, 401. The range of acid proteinase activities reported by Richards and Cuzner [40], upon which the summary of Cuzner et a1 [14] is based, is quite similar to the range of our results shown in Figure 1 and Table 2: 0 to 100 pg of BP degraded per hour per milliliter of CSF, with one value of 245 [40], as compared to 3.8 to 19.4%, or 38 to 194 pg of BP per hour per milliliter. Just how long Richards and Cuzner [40] kept their CSF samples frozen at -70°C is not stated, but we have noted that enzyme activities decrease after one week of such storage and have made a point of assaying all samples within this period.…”

Schwann cell plasminogen activator is regulated by neurons

“…Elevated levels of proteolytic enzymes have been observed in and around demyelinating plaques (Einstein et al, 1972;Govindarajan et al, 1974;Rauch et al, 1973) as well as in cerebrospinal fluid in multiple sclerosis. Although such increases have been attributed to lymphocytes and macrophages Rinne and Rikkinen, 1968;Sibley et al, 1978), astrocytes also produce and secrete plasminogen activator (Toshniwal et al, 1987) suggesting that glial cells also participate in demyelination. Additionally, neutral proteinases including plasminogen activator (Brosnan et al, 1980a) degrade myelin basic protein and cause demyelination in vivo.…”

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

“…Cuzner et a1 [ 14,401 reported "basically the same" [40] or "directly proportional" [14] results with hemoglobin and BP at pH 7.6, but the actual values reported in their [14] shows that hemoglobin was digested at p H 3.6, albeit only 5 to 10% as much as at p H 7.6. Finally, whereas the ranges of our neutral and acid proteinase activities are approximately equal with BP as substrate (see Fig 1, Table 2 ) , the ranges reported by Rinne and Riekkinen [43] appear at least slightly different when hemoglobin was used as a substrate, with higher acid proteinase activities.…”

“…Of the several studies of proteolytic enzymes in CSF [14, 16,38,40,42,43], one [42] concerns only CSF pooled from normal volunteers, and another [38] considers only acid proteinase inhibitors; neither provides data which can be compared with the present results. Rinne and Riekkinen [43] reported acid and neutral proteinase activities using hemoglobin as substrate, and Cuzner et a1 114,16,401 presented only acid proteinase activities using BP as substrate.…”

“…Rinne and Riekkinen [43] reported acid and neutral proteinase activities using hemoglobin as substrate, and Cuzner et a1 114,16,401 presented only acid proteinase activities using BP as substrate. It is not clear just how comparable the results with the two substrates are.…”

“…Although statistically significant differences in the means of results obtained with CSF from patients with acute MS have been reported, especially for neutral proteinase [43], the biological and differential diagnostic significances are obscured by the great overlap in individual results, especially for acid proteinase [ 14, 401. The range of acid proteinase activities reported by Richards and Cuzner [40], upon which the summary of Cuzner et a1 [14] is based, is quite similar to the range of our results shown in Figure 1 and Table 2: 0 to 100 pg of BP degraded per hour per milliliter of CSF, with one value of 245 [40], as compared to 3.8 to 19.4%, or 38 to 194 pg of BP per hour per milliliter. Just how long Richards and Cuzner [40] kept their CSF samples frozen at -70°C is not stated, but we have noted that enzyme activities decrease after one week of such storage and have made a point of assaying all samples within this period.…”

Schwann cell plasminogen activator is regulated by neurons

“…Elevated levels of proteolytic enzymes have been observed in and around demyelinating plaques (Einstein et al, 1972;Govindarajan et al, 1974;Rauch et al, 1973) as well as in cerebrospinal fluid in multiple sclerosis. Although such increases have been attributed to lymphocytes and macrophages Rinne and Rikkinen, 1968;Sibley et al, 1978), astrocytes also produce and secrete plasminogen activator (Toshniwal et al, 1987) suggesting that glial cells also participate in demyelination. Additionally, neutral proteinases including plasminogen activator (Brosnan et al, 1980a) degrade myelin basic protein and cause demyelination in vivo.…”