Effect of recombinant human interleukin 2 on neutrophil adherence to endothelial cells in vitro.
Human neutrophils were demonstrated to possess interleukin-2 receptor (IL-2R) beta and gamma chains, not alpha chain and the binding of IL-2 to the IL-2R beta chain on neutrophils plays an important regulatory role in neutrophil functions. We have investigated in this study the hypothesis that recombinant human IL-2 (rhIL-2) can directly activate human neutrophils and increase their adherence to human umbilical vein endothelial cells (HUVEC). In an in vitro microtiter adherence assay, rhIL-2 significantly stimulated neutrophil adherence to HUVEC in a dose- and time-dependent manner, rhILI-2 concentration at 2000 u/ml and 2 hour incubation gave the best neutrophil stimulation. Treatment of neutrophils with rhIL-2 increased the expression of adhesion molecule CD18. Pretreatment of the stimulated neutrophils with a blocking monoclonal antibody to CD18 decreased but not completely blocked the adherence of neutrophils to HUVEC. These data suggest than rhIL-2 can directly stimulate and increase neutrophil adherence to HUVEC by enhancing the expression of CD18 and possibly other adhesion molecules on neutrophil surface. This may be a critical step in the early stage of the vascular leak syndrome (VLS) associated with high dose IL-2 therapy.
Li
J
J
Department of Medical Physics, Hamilton Regional Cancer Center, Hamilton, Ontario, Canada.
Gyorffy
S
S
Lee
S
S
Kwok
C S
CS
D000328:Adult; D018821:CD18 Antigens / Q000502:physiology; D019559:Capillary Leak Syndrome / Q000139:chemically induced / Q000503:physiopathology; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000502:physiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D007376:Interleukin-2 / Q000009:adverse effects / Q000494:pharmacology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects*; D015375:Receptors, Interleukin-2 / Q000187:drug effects / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D014471:Umbilical Veins
D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D009240:N-Formylmethionine Leucyl-Phenylalanine