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IgA-mediated inhibition of human leucocyte function by interference with Fc gamma and C3b receptors
1Department of Oral Microbiology, School of Dentistry, Nippon Dental University, Niigata, Japan.
Insights
Human immunoglobulin A (IgA) from colostrum and serum inhibits polymorphonuclear leucocytes (PML) function, including bacterial phagocytosis and chemiluminescence response. This IgA-mediated suppression is linked to reduced Fc and C3b receptors on PML.
Area of Science:
- Immunology
- Cellular Biology
- Microbiology
Background:
- Polymorphonuclear leucocytes (PML) are crucial for innate immunity, responding to bacterial stimuli via phagocytosis and chemiluminescence (CL).
- Immunoglobulin A (IgA) is a key antibody in mucosal immunity, but its direct effects on neutrophil function are less understood.
Purpose of the Study:
- To investigate the inhibitory effects of human colostrum and serum IgA on PML's chemiluminescence response and phagocytosis.
- To determine IgA's impact on PML's response to Staphylococcus epidermidis and formylmethionyl-leucyl-phenylalanine (FMLP).
- To elucidate the mechanism of IgA inhibition, focusing on its effect on Fc and C3b receptors (CR1).
Main Methods:
- Studied luminol-mediated chemiluminescence (CL) of human PML stimulated by Staphylococcus epidermidis and FMLP.
- Assessed phagocytic activity of PML in the presence of varying concentrations of IgA.
- Quantified Fc and C3b receptors (CR1) on PML using rosette formation and immunofluorescence assays.
Main Results:
- Human IgA, from both colostrum and serum, dose-dependently inhibited the CL response and phagocytosis of PML to Staphylococcus epidermidis.
- IgA preincubation enhanced inhibition, while IgA removal allowed response recovery; IgA did not inhibit bacteria directly.
- IgA significantly reduced the expression of Fc and C3b receptors (CR1) on PML, impairing IgG binding and bacterial phagocytosis.
Conclusions:
- Human IgA exerts an inhibitory effect on key functions of polymorphonuclear leucocytes (PML), including phagocytosis and chemiluminescence.
- The suppressive mechanism involves the downregulation of Fc and C3b receptors (CR1) on the PML surface.
- These findings highlight a novel immunomodulatory role for IgA in regulating neutrophil-mediated innate immune responses.
Abstract:
The inhibitory effects of IgA from human colostrum, and IgA1 and IgA2 from human serum on the chemiluminescence (CL) response and phagocytosis of polymorphonuclear leucocytes (PML) to Staphylococcus epidermidis and the CL response to formylmethionyl-leucyl-phenylalanine (FMLP) were studied. The dose-dependent inhibition of the luminol-mediated CL response of human PML to the bacteria was observed in the presence of more than 0.1 mg/ml IgA from both colostrum and serum. The preincubation of PML with a solution of IgA enhanced the suppressive effect of IgA on the cells. Removal of IgA from the reaction mixture after preincubation resulted in recovery, with time, of the response of PML to the bacteria. The bacteria treated with IgA did not give rise to any inhibition of the response. The CL response of PML to FMLP was not affected by the presence of IgA in the reaction mixture. The decrease of phagocytic activity of PML in the presence of IgA resulted in a decrease of NADPH oxidase activity of PML after stimulation with the bacteria as compared with the absence of IgA. The effect of IgA on the receptors of Fc and C3b (CR1) on the surface of PML was measured by monitoring erythrocyte-antibody (EA) or erythrocyte-antibody-complement (EAC) rosette formation and by direct and indirect immunofluorescence techniques using anti-CR1 antibody and Fc-specific antibodies. The presence of IgA in the reaction mixture led to a quantitative decrease in CR1 and the ability to bind IgG to the surface of PML.