Anti-CD45 isoform antibodies enhance phagocytosis and gene expression of IL-8 and TNF-alpha in human neutrophils by differential suppression on protein tyrosine phosphorylation and p56lck tyrosine kinase.
To determine the biological functions of membrane expressed CD45 isoforms on polymorphonuclear neutrophils (PMN), the monoclonal IgG F(ab')2 antibody against CD45, CD45RA or CD45RO was used as surrogate ligand for binding with these molecules on PMN. We found 99.5 +/- 3.2%, 42.3 +/- 5.8% and 96.7 +/- 2.6% PMN expressed CD45, CD45RA and CD45RO molecules on the cell surface, respectively. The interaction of CD45, CD45RA or CD45RO with its specific antibody on PMN enhanced phagocytosis markedly (34-83% increase), mainly via increased expression of complement receptor type 3 (CR3, CD11b) on the cells. The production of IL-8 by PMN was also increased significantly after binding with antibodies (anti-CD45 > anti-CD45RO > anti-CD45RA). Anti-CD45RA and anti-CD45RO, but not anti-CD45, enhanced TNF-alpha mRNA expression and decreased protein tyrosine phosphorylation of PMN. However, only anti-CD45RO suppressed Src family protein tyrosine kinase p56lck expression in the cells. These results suggest that the cross-linking of CD45 isoforms by their specific antibodies stimulated different PMN activities by differential suppression on protein tyrosine phosphorylation and Src family tyrosine kinase p56lck.
Yu
C- L
C
Department of Medicine, National Taiwan University Hospital, Taipei, Taiwan. clyu@ha.mc.ntu.edu.tw
Yu
H-S
HS
Sun
K-H
KH
Hsieh
S-C
SC
Tsai
C-Y
CY
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D000918:Antibody Specificity; D000954:Antigens, Surface / Q000276:immunology / Q000502:physiology; D004790:Enzyme Induction / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D017493:Leukocyte Common Antigens / Q000276:immunology / Q000502:physiology*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008214:Lymphocytes / Q000187:drug effects; D016177:Macrophage-1 Antigen / Q000096:biosynthesis / Q000235:genetics; D009000:Monocytes / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology; D010587:Phagocytosis / Q000187:drug effects* / Q000502:physiology; D010766:Phosphorylation; D020033:Protein Isoforms / Q000276:immunology / Q000502:physiology*; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D007140:Immunoglobulin Fab Fragments; D016209:Interleukin-8; D016177:Macrophage-1 Antigen; D020033:Protein Isoforms; D014409:Tumor Necrosis Factor-alpha; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D017493:Leukocyte Common Antigens