Reduced protein tyrosine phosphatase (PTPase) activity of CD45 on peripheral blood lymphocytes in patients with systemic lupus erythematosus (SLE).
To disclose the mechanism of aberrant function of peripheral blood lymphocytes (PBL) in SLE, we focused on the catalytic function of CD45, and determined the CD45 PTPase activity in SLE patients. The sample population consisted of 32 SLE patients with different disease activity. PTPase activity of cell lysates immunoprecipitated by anti-CD45 MoAb was assayed against phosphotyrosine analogue PNPP, followed by measuring the release of para-nitro phenol at 410 nm. CD45 PTPase activity of PBL was significantly decreased in SLE patients, compared with that of normal controls and patients with systemic sclerosis (964 +/- 265, 1202 +/- 172, 1210 +/- 125, respectively; SLE versus normal, P<0.05). It was correlated with SLE Disease Activity Index (SLEDAI) score (r = 0.597, P = 0.0006), but not with the dose of prednisolone (r = 0.214, P = 0.2657), indicating that CD45 PTPase activity became reduced when the disease was active, but it was not affected by prednisolone. Moreover, it was not corrected by in vitro culture with or without stimulation. The expression of CD45 on PBL was comparable between normal and SLE, raising a possibility that it may be due to aberrant regulation of catalytic function of CD45 in SLE. Given the evidence that tyrosine phosphorylation of cellular proteins by tyrosine kinases and phosphatases is one of the key biochemical events in the signal transduction pathway, the decreased CD45 PTPase activity in SLE may account for the defective signal transduction via TCR/CD3, leading to dysregulated effector function of the lymphocytes.
Takeuchi
T
T
Second Department of Internal Medicine, Saitama Medical Centre, Kawagoe-shi, Japan.
Pang
M
M
Amano
K
K
Koide
J
J
Abe
T
T
D000328:Adult; D000814:Aniline Compounds / Q000378:metabolism; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy / Q000201:enzymology* / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D008875:Middle Aged; D009596:Nitrophenols / Q000032:analysis / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000378:metabolism; D010766:Phosphorylation; D011233:Precipitin Tests; D011239:Prednisolone / Q000494:pharmacology / Q000627:therapeutic use; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D012595:Scleroderma, Systemic / Q000201:enzymology / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology
D000814:Aniline Compounds; D000893:Anti-Inflammatory Agents; D009596:Nitrophenols; D009943:Organophosphorus Compounds; C068798:4-aminophenylphosphate; D011239:Prednisolone; D017493:Leukocyte Common Antigens; D017027:Protein Tyrosine Phosphatases; C024836:4-nitrophenol