Continued tumor necrosis factor receptor expression by trauma patients' monocytes (Mphi) despite TNF alpha secretion.
In investigating various mechanisms for continued elevated tumor necrosis factor alpha (TNF alpha) production in trauma patients' monocytes (Mphi), we examined TNF receptor (TNFR) levels on the patients' Mphi as a possible altered pathway leading to continued autocrine TNF alpha stimulation. Mphi TNFR synthesis and shedding are both increased as TNF alpha protein production increases. In fatal meningococcal infections, TNFR shedding fails to pace TNF alpha production. Here, isolated normal and trauma patients' Mphi (injury severity score greater than 30), were examined by flow cytometry using phycoerythrin-labeled TNF alpha to detect increased or decreased TNFR expression concomitant to Mphi production of secreted TNF alpha (as measured in the LM bioassay). Immunoaberrant patients (mitogen proliferation depressed) had reduction in detectable TNF alpha binding by their TNFR, while Mphi from immunocompetent (normal mitogen response) trauma patients' Mphi had a TNFR expression intensity comparable to normals' Mphi. Upon in vitro stimulation of TNF alpha (IFN gamma + muramyl dipeptide) normals' and immunocompetent patients' MO TNFR expression is decreased for the entire 18 h period during which secreted TNF alpha is produced, but immunoaberrant trauma patients' Mphi increased their TNFR expression, while concomitantly producing both secreted and cell-associated TNF alpha protein. Patients' Mphi with highly elevated TNF alpha levels are still expressing high levels of TNFR and capable of auto-stimulating TNF alpha production. This elevated TNFR expression could be due to reduced shedding, overproduction of TNFR, or both.
Miller-Graziano
C L
CL
Department of Surgery, University of Massachusetts Medical Center, Worcester 01655, USA.
Kodys
K
K
Gonzalez
F
F
Fudem
G M
GM
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology; D000328:Adult; D000368:Aged; D002056:Burns / Q000097:blood* / Q000276:immunology / Q000473:pathology; D002478:Cells, Cultured; D005260:Female; D005453:Fluorescence; D006801:Humans; D016867:Immunocompromised Host; D007371:Interferon-gamma / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis* / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism*; D014947:Wounds and Injuries / Q000097:blood* / Q000276:immunology / Q000473:pathology
D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D007371:Interferon-gamma