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P‐selectin‐dependent leukocyte recruitment and intestinal mucosal injury induced by lactoferrin
Author(s) -
Kurose Iwao,
Yamada Tamaki,
Wolf Robert,
Granger D. Neil
Publication year - 1994
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.55.6.771
Subject(s) - lactoferrin , intravital microscopy , myeloperoxidase , fluorescein isothiocyanate , immunology , granulocyte , biology , p selectin , inflammation , albumin , vascular permeability , intestinal mucosa , pathology , medicine , endocrinology , biochemistry , microcirculation , platelet , platelet activation , physics , quantum mechanics , fluorescence
Plasma concentrations of lactoferrin relevant to an inflammatory response are known to elicit leukocyteendothelial cell adhesion in mesenteric venules. The objectives of this study were (1) to determine whether exogenously administered lactoferrin causes microvascular and mucosal injury in rat intestine and (2) to assess the contribution of adherent leukocytes to a lactoferrinmediated injury process. Mucosal myeloperoxidase (MPO) activity and vascular protein clearance were monitored in the distal intestine of male Sprague‐Dawley rats. Macroscopic erosive lesions of the mucosa and increases in mucosal MPO and intestinal vascular protein were observed 2 h following the lactoferrin infusion, results consistent with granulocyte accumulation and microvascular protein leakage. These lactoferrin‐induced alterations were significantly attenuated in animals pretreated with a monoclonal antibody (mAb) directed against P‐selectin but not by an E‐selectin‐specific mAb. In another series of experiments, leukocyte adherence/emigration and leakage of fluorescein isothiocyanate (FITC)‐labeled albumin were measured in rat mesenteric venules using intravital video microscopy. Lactoferrin elicited increases in both leukocyte adhesion/emigration and albumin extravasation, which were attenuated by mAbs directed against P‐selectin but not E‐selectin. These observations indicate that (1) the lactoferrin released by activated neutrophils may lead to significant microvascular and mucosal injury or dysfunction and (2) the lactoferrininduced injury is related to P‐selectin‐mediated adhesion of leukocytes to microvascular endothelium. Our results raise the possibility that neutrophil‐derived lactoferrin contributes to the inflammatory response by promoting further granulocyte accumulation and activation and that mAbs to P‐selectin may be therapeutically beneficial in inflammatory disorders. J. Leukoc. Biol. 55: 771–777; 1994.