Leukotriene B4 binding to human neutrophils

Journal Article · Sat Dec 01 04:00:00 EST 1984 · Prostaglandins; (United States)

DOI:https://doi.org/10.1016/0090-6980(84)90038-8· OSTI ID:5609706

Lin, A H; Ruppel, P L; Gorman, R R

(/sup 3/H) Leukotriene B4 (LTB4) binds concentration dependently to intact human polymorphonuclear leukocytes (PMN's). The binding is saturable, reaches equilibrium in 10 min at 4 degrees C, and is readily reversible. Mathematical modeling analysis reveals biphasic binding of (/sup 3/H) LTB4 indicating two discrete populations of binding sites. The high affinity binding sites have a dissociation constant of 0.46 X 10(-9)M and Bmax of 1.96 X 10(4) sites per neutrophil; the low affinity binding sites have a dissociation constant of 541 X 10(-9)M and a Bmax of 45.16 X 10(4) sites per neutrophil. Competitive binding experiments with structural analogues of LTB4 demonstrate that the interaction between LTB4 and the binding site is stereospecific, and correlates with the relative biological activity of the analogs. At 25 degrees C (/sup 3/H) LTB4 is rapidly dissociated from the binding site and metabolized to 20-OH and 20-COOH-LTB4. Purification of neutrophils in the presence of 5-lipoxygenase inhibitors significantly increases specific (/sup 3/H) LTB4 binding, suggesting that LTB4 is biosynthesized during the purification procedure. These data suggest that stereospecific binding and metabolism of LTB4 in neutrophils are tightly coupled processes.

• Research Organization: Upjohn Co., Kalamazoo, MI
• OSTI ID: 5609706
• Journal Information: Prostaglandins; (United States), Journal Name: Prostaglandins; (United States) Vol. 28:6; ISSN PRGLB
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AFFINITY
ANIMALS
ARACHIDONIC ACID
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CARBOXYLIC ACIDS
CHEMICAL BONDS
ENZYMES
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LEUKOCYTES
MAMMALS
MAN
MATERIALS
MATHEMATICAL MODELS
METABOLISM
METABOLITES
MONOCARBOXYLIC ACIDS
NEUTROPHILS
ORGANIC ACIDS
ORGANIC COMPOUNDS
OXIDOREDUCTASES
OXYGENASES
PRIMATES
PURIFICATION
REACTION KINETICS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES