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Two functional domains in the phagocyte membrane glycoprotein Mo1 identified with monoclonal antibodies
Abstract:
Granulocytes from patients genetically deficient in the leukocyte glycoprotein family, Mo1, LFA-1, and Leu-M5 (P150,94), have defective complement receptor type III (CR3) activity as well as abnormal adhesion-dependent functions such as spreading, chemotaxis, and phagocytosis. To determine the contribution of the Mo1 heterodimer deficiency to the various functional aberrations observed in deficient granulocytes, we mapped the functional domains of Mo1 using several monoclonal antibodies to this molecule. In addition to iC3b binding, two granulocyte adhesion functions were examined: Cell spreading on plastic coverslips and chemotaxis. One monoclonal antibody to Mo1, 44, inhibits all three functions. Other monoclonal antibodies (903, Leu-15, and OKM10) inhibit iC3b binding to granulocytes but have no effect on cell spreading and/or chemotaxis. Another antibody, 904, has no significant inhibition of iC3b binding but inhibits spreading on plastic and chemotaxis. These studies suggest the presence of two functional domains in Mo1: one involved in iC3b binding and the other in enhancing certain granulocyte adhesion-dependent functions.
Insights
Deficiencies in Mo1, a leukocyte glycoprotein, impair granulocyte functions. Researchers mapped Mo1
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Granulocytes lacking leukocyte glycoproteins Mo1, LFA-1, and Leu-M5 exhibit impaired complement receptor type III (CR3) activity.
- These deficiencies lead to abnormal adhesion-dependent functions, including cell spreading, chemotaxis, and phagocytosis.
- The Mo1 heterodimer is crucial for these granulocyte functions, but its specific functional domains require detailed mapping.
Purpose of the Study:
- To elucidate the specific functional domains of the Mo1 heterodimer.
- To determine the contribution of Mo1 deficiency to observed functional aberrations in granulocytes.
- To investigate the roles of distinct Mo1 domains in iC3b binding and adhesion-dependent functions.
Main Methods:
- Utilized monoclonal antibodies targeting the Mo1 molecule to map its functional domains.
- Assessed iC3b binding activity of granulocytes.
- Examined granulocyte adhesion functions: cell spreading on plastic and chemotaxis.
Main Results:
- Monoclonal antibody 44 inhibited iC3b binding, cell spreading, and chemotaxis, indicating a broad functional role.
- Antibodies 903, Leu-15, and OKM10 inhibited iC3b binding but did not affect cell spreading or chemotaxis.
- Antibody 904 showed no significant inhibition of iC3b binding but impaired cell spreading and chemotaxis.
Conclusions:
- The Mo1 heterodimer possesses at least two distinct functional domains.
- One domain is responsible for iC3b binding.
- A separate domain enhances specific granulocyte adhesion-dependent functions, such as spreading and chemotaxis.