title: Biochemical basis of HLA-DR and CR3 modulation on human peripheral blood monocytes by lipopolysaccharide.
abstract: The biochemical events leading to enhanced membrane expression of HLA-DR and CR3 by human peripheral blood monocytes (MO) following exposure to bacterial lipopolysaccharide (LPS) were examined. In a previous study we demonstrated that an increase in intracellular calcium was necessary, but not sufficient, for MO to increase membrane expression of both antigens within 1 hr of addition of LPS. The present study was initiated to examine the other biochemical requirements which lead to the MO response to LPS. Enhanced expression of both antigens following addition of LPS was dependent on microfilament function, but independent of microtubule function and of protein synthesis. Inhibition of formation of cyclooxygenase or lipoxygenase metabolites of arachidonic acid had no effect on HLA-DR or CR3 modulation by LPS. A role for phosphatidylinositol metabolism was suggested by the inhibition of the MO response to LPS by dibutyryl cAMP and theophylline and by the enhanced expression of both antigens following addition of phorbol diesters. However, H-7, a putative inhibitor of protein kinase C, did not alter the MO response to LPS or phorbol diesters. These results suggest that LPS enhances expression of HLA-DR and CR3 by inducing redistribution of these antigens from an intracellular pool. The data also support a role for the generation of hydrolysis products of phosphatidylinositol, leading to calcium redistribution and activation of protein kinase C or other kinases, in the MO response to LPS.
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D008841:Actin Cytoskeleton / Q000502:physiology; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D006681:HLA-D Antigens / Q000096:biosynthesis*; D006684:HLA-DR Antigens / Q000096:biosynthesis*; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D010716:Phosphatidylinositols / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology; D011951:Receptors, Complement / Q000096:biosynthesis*; D017463:Receptors, Complement 3b; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology
chemical_list: D006681:HLA-D Antigens; D006684:HLA-DR Antigens; D007546:Isoquinolines; D008070:Lipopolysaccharides; D010716:Phosphatidylinositols; D010879:Piperazines; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; C036757:lipopolysaccharide B; D003994:Bucladesine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D013806:Theophylline; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium