Molecules and structures involved in the adhesion of natural killer cells to vascular endothelium.
The present study was designed to define molecules and structures involved in the interaction of natural killer (NK) cells with the vascular endothelium in vitro. Resting and interleukin 2 (IL-2)-activated NK cells were studied for their capacity to adhere to resting and IL-1-treated human umbilical vein endothelial cells (EC). In the absence of stimuli, NK cells showed appreciable adhesion to EC, with levels of binding intermediate between polymorphs and monocytes. The binding ability was increased by pretreatment of NK cells with IL-2. Using the appropriate monoclonal antibody, the beta 2 leukocyte integrin CD18/CD11a was identified as the major adhesion pathway of NK cells to unstimulated EC. Activation of EC with IL-1 increased the binding of NK cells. In addition to the CD18-CD11a/intercellular adhesion molecule pathway, the interaction of resting or IL-2-activated NK cells to IL-1-activated EC involved the VLA-4 (alpha 4 beta 1)-vascular cell adhesion molecule 1 receptor/counter-receptor pair. No evidence for appreciable involvement of endothelial-leukocyte adhesion molecule was obtained. Often, NK cells interacted either with the culture substrate or with the EC surface via dot-shaped adhesion structures (podosomes) protruding from the ventral surface and consisting of a core of F-actin surrounded by a ring of vinculin and talin. The identification of molecules and microanatomical structures involved in the interaction of NK cells with EC may provide a better understanding of the regulation of NK cell recruitment from blood, their extravasation, and their migration to tissues.
Allavena
P
P
Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
Paganin
C
C
Martin-Padura
I
I
Peri
G
G
Gaboli
M
M
Dejana
E
E
Marchisio
P C
PC
Mantovani
A
A
D000911:Antibodies, Monoclonal / Q000276:immunology; D018821:CD18 Antigens; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D039001:Integrin alpha Chains; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000166:cytology*; D007700:Kinetics; D008213:Lymphocyte Activation / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D015388:Organelles / Q000502:physiology*; D016028:Receptors, Leukocyte-Adhesion / Q000502:physiology; D016029:Receptors, Very Late Antigen / Q000502:physiology
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; C063493:CDw49d; D015815:Cell Adhesion Molecules; D039001:Integrin alpha Chains; D007375:Interleukin-1; D007376:Interleukin-2; D016169:Lymphocyte Function-Associated Antigen-1; D016028:Receptors, Leukocyte-Adhesion; D016029:Receptors, Very Late Antigen