Biomaterial Database

Alteration of chloroquine accumulation in human polymorphonuclear leucocytes under inflammatory conditions. 1987

M Raghoebar, and W B van den Berg, and C A van Ginneken

The present study concerns the established antirheumatic drug chloroquine (CQ) in relation to a possible target for drug therapy, the polymorphonuclear leucocyte (PMN). Its primary aim was to find out whether inflammatory conditions would influence the cell association of CQ. After a suitable ligand-binding assay was developed to measure the cellular association of CQ, the normal characteristics of the cellular transport of CQ were determined. The effect of the inflammatory conditions on CQ cell association was investigated with peripheral PMNs from rheumatoid arthritis (RA) patients, and with normal PMNs, in the absence and presence of the soluble cell-stimulators phorbol ester and chemotactic peptide. Under inflammatory conditions the intracellular concentration of CQ is reduced. This decrease is explained by three possibilities which are involved in cell activation: the leucocyte volume expansion, the cytoplasmic or lysosomal pH changes, and the exocytic release of the granules (degranulation). Our results suggest that this decrease will adversely affect the therapeutic effects, if the mode of anti-inflammatory action of CQ is related to the intracellular drug concentrations.

UI	MeSH Term	Description	Entries
D007249	Inflammation	A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.	Innate Inflammatory Response,Inflammations,Inflammatory Response, Innate,Innate Inflammatory Responses
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008247	Lysosomes	A class of morphologically heterogeneous cytoplasmic particles in animal and plant tissues characterized by their content of hydrolytic enzymes and the structure-linked latency of these enzymes. The intracellular functions of lysosomes depend on their lytic potential. The single unit membrane of the lysosome acts as a barrier between the enzymes enclosed in the lysosome and the external substrate. The activity of the enzymes contained in lysosomes is limited or nil unless the vesicle in which they are enclosed is ruptured or undergoes MEMBRANE FUSION. (From Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed).	Autolysosome,Autolysosomes,Lysosome
D009504	Neutrophils	Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.	LE Cells,Leukocytes, Polymorphonuclear,Polymorphonuclear Leukocytes,Polymorphonuclear Neutrophils,Neutrophil Band Cells,Band Cell, Neutrophil,Cell, LE,LE Cell,Leukocyte, Polymorphonuclear,Neutrophil,Neutrophil Band Cell,Neutrophil, Polymorphonuclear,Polymorphonuclear Leukocyte,Polymorphonuclear Neutrophil
D002738	Chloroquine	The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses.	Aralen,Arechine,Arequin,Chingamin,Chlorochin,Chloroquine Sulfate,Chloroquine Sulphate,Khingamin,Nivaquine,Sulfate, Chloroquine,Sulphate, Chloroquine
D005089	Exocytosis	Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the CELL MEMBRANE.
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006863	Hydrogen-Ion Concentration	The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH	pH,Concentration, Hydrogen-Ion,Concentrations, Hydrogen-Ion,Hydrogen Ion Concentration,Hydrogen-Ion Concentrations