Behavior of stimulated leukocytes in the pulmonary microcirculation of perfused rat lungs.
To investigate the dynamics of activated leukocytes and the roles of CD18-ICAM-1 pathway, we examined the effects of rat IL-8 and monoclonal antibodies (mAbs) against CD18 and ICAM-1 on the behavior of leukocytes in microvessels of perfused rat lungs. Specific pathogen free male Sprague-Dawley rats were used. Perfused rat lungs were prepared so as to obtain stable physiological shear rates. We used a confocal laser scanning microscope equipped with a high speed video analysis system to visualize pulmonary microcirculation. Rat leukocytes were activated with rat IL-8. No rolling leukocytes were observed in either pulmonary arterioles or venules, and leukocytes were sequestered in capillaries. The majority of unstimulated capillary leukocytes moved smoothly. About 50% of stimulated leukocytes, however, showed a transient cessation of movement in pulmonary capillaries. Rat IL-8 decreased the relative leukocyte velocities against mean blood velocities in capillaries (45%) and venules (65%), and increased intracapillary neutrophils. Anti-CD18 and anti-ICAM-1 mAbs attenuated these changes. These results suggest that unique features exist in the interaction between activated leukocytes and pulmonary microvessels, and that CD18-ICAM-1-dependent capillary sequestration is one of the major mechanisms by which activated leukocytes accumulate in lungs.
Aoki
T
T
Department of Internal Medicine, Kitasato Institute Hospital, Tokyo, Japan.
Suzuki
Y
Y
Nishio
K
K
Suzuki
K
K
Miyata
A
A
Mori
M
M
Takasugi
T
T
Fujita
H
H
Tsumura
H
H
Ishimura
Y
Y
Suematsu
M
M
Yamaguchi
K
K
D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001783:Blood Flow Velocity / Q000187:drug effects; D018821:CD18 Antigens / Q000276:immunology / Q000502:physiology; D003911:Dextrans; D004912:Erythrocytes / Q000502:physiology; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives; D005456:Fluorescent Dyes; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000502:physiology; D016209:Interleukin-8 / Q000494:pharmacology; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology*; D008168:Lung / Q000098:blood supply*; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology*; D010477:Perfusion; D011652:Pulmonary Circulation / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D003911:Dextrans; D005456:Fluorescent Dyes; D016209:Interleukin-8; D011994:Recombinant Proteins; C015219:fluorescein isothiocyanate dextran; D018799:Intercellular Adhesion Molecule-1; D016650:Fluorescein-5-isothiocyanate