IL-4 inhibits binding and cytotoxicity of NK cells to vascular endothelium.
We investigated the influence of IL-4 on the interaction between Natural Killer (NK) cells and vascular endothelial cells (EC). Pretreatment of NK cells with IL-4 inhibited the adhesion of NK cells on resting or IL-1-activated EC. The inhibitory action of IL-4 was observed on both unstimulated NK cells as well as on cells concomitantly activated with IL-2 or with phorbol ester. IL-4 also inhibited the cytotoxicity of IL-2 activated NK cells on EC. Binding of NK cells to vascular EC involves the LFA1/ICAM-1 and 2, and VLA-4/VCAM-1 adhesion pathway. Anti-CD18 mAb had a lower inhibitory effect in IL-4-treated NK cells compared to control. The levels of inhibition with resting vs IL-1-activated EC, as well as antibody blocking experiments, suggested that IL-4 exerts an inhibitory influence predominantly on the beta 2-integrin (CD18)-dependent adhesion pathway; nevertheless IL-4 did not affect the expression of CD18/CD11a and VLA-4 on the NK cell surface, as assessed by flow cytometry. NK cells are potent producers of IFN-gamma and there is evidence that they play a role in orienting immunity to the TH1-type responses. The inhibition by IL-4 of NK cell binding to EC and subsequent recruitment and activation may thus contribute to development of TH2 responses.
Paganin
C
C
Department of Immunology, Mario Negri Institute, Milano, Italy.
Matteucci
C
C
Cenzuales
S
S
Mantovani
A
A
Allavena
P
P
D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000032:analysis / Q000096:biosynthesis; D018845:CD11 Antigens; D018821:CD18 Antigens; D002448:Cell Adhesion / Q000187:drug effects*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D016028:Receptors, Leukocyte-Adhesion / Q000032:analysis / Q000096:biosynthesis; D016029:Receptors, Very Late Antigen / Q000032:analysis / Q000096:biosynthesis; D014471:Umbilical Veins
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018845:CD11 Antigens; D018821:CD18 Antigens; D007376:Interleukin-2; D016028:Receptors, Leukocyte-Adhesion; D016029:Receptors, Very Late Antigen; D015847:Interleukin-4