Role of CD18-ICAM-1 in the entrapment of stimulated leukocytes in alveolar capillaries of perfused rat lungs.
This study aimed to examine the behavior of stimulated leukocytes in the pulmonary microcirculation. The leukocyte-endothelium interaction was visualized under physiological shear rates in perfused rat lungs using high-speed confocal laser video microscopy. Leukocytes labeled with carboxyfluorescein were stimulated with cytokine-induced neutrophil chemoattractant (CINC/gro), which caused L-selectin shedding and inverse upregulation of CD18. Neither unstimulated nor stimulated leukocytes exhibited rolling in either pulmonary arterioles or venules, whereas both were sequestered in capillaries. Approximately 50% of stimulated leukocytes showed a transient cessation of movement in pulmonary capillaries. The CINC/ gro stimulation, which inhibited leukocyte rolling and adhesion to mesenteric venules, reduced leukocyte velocity and increased leukocytes in pulmonary capillaries. Pretreatment with monoclonal antibodies against intercellular adhesion molecule-1 (ICAM-1) or CD18 attenuated these changes. Confocal microfluorography revealed constitutive expression of ICAM-1 not only in venules but also abundantly in capillary networks. These results suggest that selectin-independent, CD18-ICAM-1-dependent capillary sequestration is one of the major mechanisms by which activated leukocytes accumulate in the lungs.
Aoki
T
T
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Suzuki
Y
Y
Nishio
K
K
Suzuki
K
K
Miyata
A
A
Iigou
Y
Y
Serizawa
H
H
Tsumura
H
H
Ishimura
Y
Y
Suematsu
M
M
Yamaguchi
K
K
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001160:Arterioles / Q000502:physiology; D018821:CD18 Antigens / Q000096:biosynthesis / Q000502:physiology*; D002196:Capillaries / Q000502:physiology*; D054360:Chemokine CXCL1; D018925:Chemokines / Q000502:physiology; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004730:Endothelium, Vascular / Q000502:physiology*; D004912:Erythrocytes / Q000502:physiology; D006133:Growth Substances / Q000502:physiology; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8 / Q000494:pharmacology; D019041:L-Selectin / Q000502:physiology; D008297:Male; D018715:Microscopy, Video; D011650:Pulmonary Alveoli / Q000098:blood supply*; D011652:Pulmonary Circulation / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014699:Venules / Q000502:physiology
D000906:Antibodies; D018821:CD18 Antigens; D054360:Chemokine CXCL1; D018925:Chemokines; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C513297:Cxcl1 protein, rat; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8; D018799:Intercellular Adhesion Molecule-1; D019041:L-Selectin