L-selectin is required for fMLP- but not C5a-induced margination of neutrophils in pulmonary circulation.
To study the role of L-selectin in neutrophil (PMN) margination and sequestration in the pulmonary microcirculation, maximally active concentrations of C5a (900 pmol/g) and N-formylmethionyl-leucyl-phenylalanine (fMLP; 0.34 pmol/g) were injected into the jugular vein of wild-type or L-selectin-deficient C57BL/6 mice. In wild-type mice administered C5a or fMLP, 92 +/- 1% and 34 +/- 9%, respectively, of peripheral blood PMN were trapped mostly in the pulmonary circulation as determined by immunohistochemistry and myeloperoxidase activity. In wild-type mice treated with F(ab')(2) fragments of the L-selectin monoclonal antibody MEL-14 or in L-selectin-deficient mice, C5a-induced neutropenia was not significantly reduced, but the decrease in peripheral PMN in response to fMLP was completely abolished, indicating that L-selectin is necessary for fMLP- but not C5a-induced pulmonary margination. Immunostained lung sections of fMLP- or C5a-treated mice showed sequestered neutrophils in alveolar capillaries with no evidence of neutrophil aggregates. We conclude that chemoattractant-induced PMN margination in the pulmonary circulation can occur by two separate mechanisms, one of which requires L-selectin.
Olson
Timothy S
TS
Department of Molecular Physiology and Medical Scientist Training Program, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA.
Singbartl
Kai
K
Ley
Klaus
K
D000818:Animals; D000911:Antibodies, Monoclonal; D002448:Cell Adhesion / Q000276:immunology; D015936:Complement C5a / Q000494:pharmacology*; D019041:L-Selectin / Q000276:immunology / Q000378:metabolism*; D008168:Lung / Q000098:blood supply / Q000201:enzymology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D009195:Peroxidase / Q000378:metabolism; D011652:Pulmonary Circulation / Q000276:immunology
D000911:Antibodies, Monoclonal; D019041:L-Selectin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015936:Complement C5a; D009195:Peroxidase