Phorbol ester causes down-regulation of CD11/CD18-independent neutrophil adherence to endothelium.
Neutrophils adhere to interleukin-1 (IL-1)-, tumour necrosis factor (TNF)- or lipopolysaccharide (LPS)-pretreated human umbilical vein endothelial cells (HEC) by CD11/CD18-dependent and independent mechanisms. We investigated CD11/CD18-independent neutrophil adherence to LPS-pretreated HEC by: (i) pretreating neutrophils with the anti-CD18 monoclonal antibody mAb 60.3; (ii) performing assays in the absence of Mg2; or (iii) using neutrophils isolated from a patient with leucocyte adhesion deficiency (CD11/CD18-deficiency). Under each of these conditions, CD11/CD18-independent neutrophil adherence to LPS-pretreated HEC was significantly greater than adherence to untreated HEC (15-18% versus 3-7%). In each case, however, stimulation of neutrophils with phorbol ester (PMA) abolished CD11/CD18-independent adherence to LPS-pretreated HEC (less than 5% adherence). Stimulation of neutrophils with bacterial chemotactic peptide (FMLP) or calcium ionophore (A23187) likewise reduced CD18-independent adherence to LPS-pretreated HEC. PMA also inhibited CD11/CD18-independent neutrophil adherence to HEC pretreated with IL-1 or TNF (80-90% inhibition). In contrast, PMA markedly enhanced CD11/CD18-dependent adherence to untreated or LPS-treated HEC. We conclude that stimulation of neutrophils with phorbol ester or other direct agonists down-regulates the CD11/CD18-independent mechanism of neutrophil adherence to IL-1, TNF- or LPS-pretreated HEC.
Dobrina
A
A
Institute of General Pathology, University of Trieste, Italy.
Carlos
T M
TM
Schwartz
B R
BR
Beatty
P G
PG
Ochs
H D
HD
Harlan
J M
JM
D015703:Antigens, CD / Q000502:physiology; D000943:Antigens, Differentiation / Q000502:physiology*; D000954:Antigens, Surface / Q000502:physiology; D018845:CD11 Antigens; D018821:CD18 Antigens; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D016028:Receptors, Leukocyte-Adhesion / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D000954:Antigens, Surface; D018845:CD11 Antigens; D018821:CD18 Antigens; D007375:Interleukin-1; D008070:Lipopolysaccharides; D016028:Receptors, Leukocyte-Adhesion; D014409:Tumor Necrosis Factor-alpha; D013755:Tetradecanoylphorbol Acetate