L-selectin is required for fMLP- but not C5a-induced margination of neutrophils in pulmonary circulation

Timothy S. Olson, Kai Singbartl, Klaus Ley

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26 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)R1245-R1252
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number4 51-4
StatePublished - 2002

All Science Journal Classification (ASJC) codes

  • General Medicine


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