Red blood cells are a sink for interleukin 8, a leukocyte chemotaxin.
IL-8 (also known as neutrophil-activating peptide 1) is recognized as a potent effector of neutrophil functions. Several different cell types that contact blood, namely T lymphocytes, monocytes, and endothelial cells, secrete this polypeptide following stimulation by cytokines, or lipopolysaccharide. Here we show that when IL-8 is added to blood it rapidly partitions from the plasma fluid to the blood cells and that erythrocytes account for the vast majority of this binding. Analysis of 125I-IL-8 binding [( ala-IL-8]77 form) to human red cells indicates a single, 5 nM Kd affinity class of binding sites, present at approximately 2,000 per red cell representing approximately 15 nmol of red cell IL-8 binding sites per liter of blood. These sites are protease sensitive. Their binding of IL-8 is rapidly reversible and does not result in receptor internalization, although bound IL-8 is resistant to extraction by pH 3 buffer at 5 degrees C. 125I-IL-8 binding to red cells was not inhibited by epidermal growth factor or interleukin 1, but was inhibited by monocyte chemotactic peptide-1, which is not a neutrophil chemotaxin, but is a member of the same family of polypeptides as IL-8. FACS analysis of IL-8-mediated mobilization of Ca2+ in neutrophils indicates that the IL-8 bound to red cells is incapable of stimulating neutrophils. Thus, red cell absorption of IL-8 may function to limit stimulation of leukocytes by IL-8 released into blood.
Department of Cardiovascular Research, Genentech, Inc., South San Francisco, California 94080.
W C
WC
Darbonne
G C
GC
Rice
M A
MA
Mohler
T
T
Apple
C A
CA
Hébert
A J
AJ
Valente
J B
JB
Baker
D000042:Absorption; D000818:Animals; D018932:Chemokine CCL2; D002630:Chemotactic Factors / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D007457:Iodine Radioisotopes; D009504:Neutrophils / Q000378:metabolism
D018932:Chemokine CCL2; D002630:Chemotactic Factors; D016209:Interleukin-8; D007457:Iodine Radioisotopes