Submitted to: Journal of Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/28/2005
Publication Date: 5/16/2005
Citation: Nagarajan, S., Fifadara, N.H., Selvaraj, P. 2005. Signal specific activation and regulation of human neutrophil FC gamma receptors. Journal of Immunology. 174(9):5423-5432.
Interpretive Summary: The ACNC has been studying the effects of diet and nutritional status on enhancement of the immune system. This study was conducted to learn more about the basic operations of the immune system prior to conducting long-term studies on various dietary factors. Neutrophils are blood cells that kill bacteria during infections. Neutrophils stick to the antibody-coated bacteria. This is mediated by a group of proteins called IgG receptors. We studied the functions of these proteins and found that they are regulated in a very complex manner. Signals recognized by the immune system have discrete effects on different types of immune cells and now that these effects are recognized. We will study the effects of dietary factors, such as those in soy and rice, to determine if and how they alter the immune response.
Technical Abstract: Fc Rs with the ITIM domain have been shown to regulate the inflammatory signal delivered by the ITAM-containing Fc Rs. In this study, we demonstrate that the function of human neutrophil Fc R type IIA (CD32A) is regulated in a distinct manner by different cell activation signals at the ligand-binding stage. Activation of neutrophils with fMLP up-regulated the ligand-binding function of CD32A, whereas PMA-mediated activation completely abolished ligand binding without altering CD32A expression. Furthermore, PMA treatment also abolished CD16B-dependent ligand binding irrespective of the level of expression. The effect of PMA was cell type specific, because the ligand-binding function of CD32A expressed on cultured cells such as K562 and CHO-CD32A transfectants was not affected by PMA. Interestingly, phorbol 12,13-dibutyrate, another phorbol ester, and IL-8 up-regulated CD32A-dependent ligand-binding function. These results demonstrate that regulation of CD32A-dependent ligand binding in human neutrophils is not only cell type specific but also activation signal specific. Moreover, these results suggest the possibility that signals delivered to neutrophils by various inflammatory stimuli can exert opposing effects on the function of human Fc Rs, representing a novel inside-out regulatory mechanism of Fc R ligand binding.