Contribution of Lysophosphatidylcholine-Treated Nonadherent Cells to Mechanism of Macrophage Activation

Abstract

Lysophosphatidylcholine (lyso-PC), a product of inflammation, stimulates (in vivo) mouse peritoneal macrophages to ingest target cells via Fc receptors. In vitro treatment of macrophages with lyso-Pc was unable to enhance ingestion activity. When a mixture of macrophages and nonadherent (B and T) cells was treated with 20 micrograms of lyso-Pc/ml for 30 min, a greatly enhanced Fc-mediated ingestion was observed at about 3 hr after treatment, suggesting that nonadherent cells contributed to activation mechanism of macrophages. The accumulated evidence suggests that treated B cells collaborated with untreated T cells in a stepwise fashion for the exchange of a signaling factor(s) for macrophage activation. When conditioned medium prepared by stepwise cultivation from treated B cells to untreated T cells was used for cultivation of untreated macrophages, a markedly enhanced Fc-mediated ingestion was observed. However, cultivation of macrophages with stepwise conditioned medium of treated T cells and untreated B cells produced no significant enhancement of phagocytic activity. Therefore, we concluded that lyso-Pc-treated B cells initiated the macrophage activation process by releasing and transmitting a signaling factor to T cells, and, in turn, the T cells modified the factor or supplied a new factor capable of the ultimate activation of macrophages for ingestion capacity. This lyso-Pc-induced factor(s) appears to be distinct from the established interleukins 1 and 2.

Retracted: Immunotherapy of HIV‐infected patients with Gc protein‐derived macrophage activating factor (GcMAF)

“…inflammation-derived macrophage activation is the process for generation of the principal macrophage activating factor [Yamamoto and Ngwenya, 1987;Ngwenya and Yamamoto, 1990;. Administration of an inflamed tissue lipid metabolite, lysophosphatidylcholine (lyso-Pc) or other lysophospholipids, to mice rapidly activates macrophages for greatly enhanced phagocytic and superoxide generating capacities [Yamamoto and Ngwenya, 1987;Homma and Yamamoto, 1990;Ngwenya and Yamamoto, 1990;Yamamoto et al, 1994].…”

“…Administration of an inflamed tissue lipid metabolite, lysophosphatidylcholine (lyso-Pc) or other lysophospholipids, to mice rapidly activates macrophages for greatly enhanced phagocytic and superoxide generating capacities [Yamamoto and Ngwenya, 1987;Homma and Yamamoto, 1990;Ngwenya and Yamamoto, 1990;Yamamoto et al, 1994]. Inflammation-derived macrophage activation process requires serum Gc protein (known as vitamin D 3 -binding protein) Yamamoto, 1993Yamamoto, , 1996 and participation of B and T lymphocytes [Ngwenya and Yamamoto, 1990;Yamamoto, 1996]. Gc protein carries one trisaccharide composed of N-acetylgalactosamine with dibranched galactose and sialic acid termini at 420 threonine residue Yamamoto, 1993Yamamoto, , 1996Yamamoto and Kumashiro, 1993].…”

Retracted: Immunotherapy of metastatic breast cancer patients with vitamin D‐binding protein‐derived macrophage activating factor (GcMAF)

“…7 Inflamed normal tissues release membranous lipid metabolites, lyso-phosphatidylcholine (lyso-Pc) and other lysophospholipids, that efficiently activate macrophages. [8][9][10][11] Inflamed cancerous tissues release lipid metabolites, lysoalkylphospholipids and alkylglycerols, because cancerous tissues contain alkylphospholipids. [11][12][13][14] Both lysoalkylphospholipids and alkylglycerols are at least 400 times more potent macrophage activating agents than lysophospholipids in terms of the minimal dosages required for optimal macrophage activation.…”

A defect in inducible β‐galactosidase of B lymphocytes in the osteopetrotic (mi/mi) mouse

“…27,28 Assay of membranous b -galactosidase on B lymphocytes The isolation procedure for splenic B cells has been described previously. 25 …”

“…The detailed procedures for isolation and cultivation of mouse peritoneal cells (mixture of adherent and nonadherent cells), enumeration of adherent cells (macrophages) and superoxide generation assay have been described previously. [25][26][27][28] For in vitro treatment of mouse peritoneal cells with lyso-Pc, resident peritoneal cells were isolated from untreated wild type or mi mutant mice. The desired cell number (6 to 9 2 l0 5 /ml) of the washed peritoneal cells were laid on 16 mm plastic culture wells and incubated at 378 in a humidified 5% CO 2 incubator for 30 min to allow macrophage adherence to the substrata.…”