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Endothelial cells upregulate eosinophil superoxide generation via VCAM‐1 expression
Author(s) -
Masaaki Nagata,
Sedgwick Jb,
Rose F. Vrtis,
Busse Ww
Publication year - 1999
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1046/j.1365-2222.1999.00506.x
Subject(s) - umbilical vein , superoxide , tumor necrosis factor alpha , cell adhesion molecule , microbiology and biotechnology , vcam 1 , adhesion , chemistry , cell adhesion , endothelial stem cell , eosinophil , endothelium , immunology , icam 1 , in vitro , biology , biochemistry , endocrinology , organic chemistry , enzyme , asthma
Background In vitro eosinophil (EOS) adhesion to recombinant human (rh)‐vascular cell adhesion molecule (VCAM)‐1 stimulates superoxide anion (O 2 − ) generation and enhances formyl‐methionyl‐leucyl phenylalanine (FMLP)‐activated O 2 − generation. Therefore, EOS adhesion via VLA‐4 to VCAM‐1 expressed on endothelium may be instrumental in the selective recruitment and function of EOS in airway inflammation. Objective We hypothesized that EOS interaction with endothelial cells expressing VCAM‐1 will undergo an enhancement in inflammatory function. Methods To determine this possibility, human umbilical vein endothelial cells (HUVEC) were stimulated with either a combination of interleukin (IL)‐4 and tumour necrosis factor (TNF)‐α (100 p M ) or medium alone for 24 h; the expression of adhesion proteins on HUVEC and their effect on EOS O 2 − generation was subsequently determined. Results As determined by both enzyme‐linked immunosorbent assay and flow cytometry, IL‐4 and TNFα acted synergistically to induce VCAM‐1 expression on HUVEC. Treating HUVEC with IL‐4/TNFα also increased EOS adhesion and primed subsequent FMLP (0.1 μ M ) activated EOS O 2 − generation. Although EOS adhesion was partially inhibited by both antiα 4 and antiβ 2 monoclonal antibodies (MoAbs), O 2 − generation was completely inhibited by either antiα 4 integrin MoAb (HP1/2) or anti‐VCAM MoAb (BBIG‐V1). Furthermore, enhanced O 2 − generation, but not adhesion, associated with IL‐4 + TNFα‐treatment of HUVEC was inhibited when EOS were treated with the platelet activating factor (PAF)‐antagonist WEB 2086 (20 μ M ), thus suggesting an involvement of PAF in priming EOS. However, paraformaldehyde fixation of IL‐4/TFN‐α treated HUVEC did not significantly alter EOS function. Conclusions These results suggest EOS adhesion to endothelial cells via an VLA‐4/VCAM–1 interaction may be important in the development of the function of this cell. Furthermore, our results suggest that modulation of EOS function involves two priming factors: EOS adhesion to HUVEC expressing VCAM‐1 and PAF.