Leukocyte rolling in venules of striated muscle and skin is mediated by P-selectin, not by L-selectin.
Leukocyte rolling in post-capillary venules is mediated by adhesion molecules of the selectin family expressed on both leukocytes (L-selectin) and endothelial cells (E- and P-selectin). With the use of intravital fluorescence microscopy, the effects of antibodies against these selectins were analyzed in the skinfold chamber model of BALB/c mice and the ear model of homozygous hairless mice (hr/hr) that permit chronic observation of striated muscle and skin microcirculation in awake animals, respectively. Mice were injected intravenously with monoclonal antibodies (MAb) to murine L-selectin and E-selectin and affinity-purified polyclonal antibodies to P-selectin. The antibodies, which are known to block cell adhesion, were tested by immunoprecipitation to selectively bind to L-, E-, or P-selectin. Leukocyte rolling was a constant finding in both microcirculation models in the absence of inflammatory stimuli. In both models, injection of anti-P-selectin antibodies completely prevented baseline leukocyte rolling over an observation period of 2 h (P < 0.01 vs. baseline), while no effects were seen after administration of either anti-L-selectin or anti-E-selectin MAb. Treatment with the isotype-matched control antibodies did not affect leukocyte rolling in either model. We conclude that leukocyte rolling in postcapillary venules of murine striated muscle and skin is a physiological process mediated via P-selectin, whereas L- and E-selectin appear not to play a significant role under these circumstances.
Nolte
D
D
Institute for Surgical Research, University of Munich, Germany.
Schmid
P
P
Jäger
U
U
Botzlar
A
A
Roesken
F
F
Hecht
R
R
Uhl
E
E
Messmer
K
K
Vestweber
D
D
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology*; D002460:Cell Line; D003429:Cross Reactions; D019040:E-Selectin; D019041:L-Selectin; D007962:Leukocytes / Q000502:physiology*; D051379:Mice; D008812:Mice, Hairless; D008807:Mice, Inbred BALB C; D008833:Microcirculation / Q000502:physiology; D008856:Microscopy, Fluorescence; D009132:Muscles / Q000098:blood supply*; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology*; D012867:Skin / Q000098:blood supply*; D014407:Tumor Cells, Cultured; D014699:Venules / Q000502:physiology*
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D019041:L-Selectin