Activation of the inflammatory response of neutrophils by Tamm-Horsfall glycoprotein.
The activation of human polymorphonuclear leukocytes (PMN) by particulate Tamm-Horsfall glycoprotein (THG) represents an interaction hitherto unrecognized. The potential pathophysiological effect of this phenomenon within the interstitium of the kidney is highlighted by the activation of the respiratory burst, as well as by comprehensive PMN degranulation. Products of the interaction are expressed in terms of phagocytosis, luminol-dependent chemiluminescence, granule marker enzyme release and arachidonic acid metabolism. Significant quantities of the primary, secondary and tertiary granule markers, myeloperoxidase, vitamin B12 binding protein and N-acetyl-beta-D-glucosaminidase, respectively, were secreted in a dose and time-dependent manner. Phagocytosis of the glycoprotein was accompanied by the generation of significant quantities of leukotriene B4. Furthermore, the ability of such a particulate ligand to activate the alternative pathway of complement clearly represents a capacity to augment the inflammatory response. Should the interaction of THG with PMN take place within the interstitium of the kidney, augmented by the deposition of complement proteins on the surface of insoluble aggregates, the resulting inflammatory response may lead to marked tissue damage and eventually result in interstitial fibrosis.
Horton
J K
JK
K.R.U.F. Institute of Renal Disease, University of Wales College of Medicine, Royal Infirmary, Wales, United Kingdom.
Davies
M
M
Topley
N
N
Thomas
D
D
Williams
J D
JD
D003170:Complement Pathway, Alternative / Q000187:drug effects; D006023:Glycoproteins / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation; D009088:Mucoproteins / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects*; D015539:Platelet Activation; D058949:Uromodulin
D006023:Glycoproteins; D009088:Mucoproteins; C548612:UMOD protein, human; D058949:Uromodulin