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The role of E‐ and P‐selectin in neutrophil and monocyte migration in adjuvant‐induced arthritis in the rat
Author(s) -
Walter Ulrike M.,
Issekutz Andrew C.
Publication year - 1997
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.1830270628
Subject(s) - l selectin , monocyte , immunology , tumor necrosis factor alpha , inflammation , arthritis , monoclonal antibody , e selectin , chemotaxis , biology , medicine , cell adhesion molecule , chemistry , adhesion , cell adhesion , antibody , receptor , organic chemistry
Abstract The role of the endothelial adhesion molecules E‐ and P‐selectin in leukocyte accumulation in arthritis is not known. We investigated this role in rat adjuvant arthritis by employing adhesion function‐blocking monoclonal antibodies (mAb) to rat P‐ and E‐selectin. The acute migration (2 h) of radiolabeled rat blood neutrophils and monocytes to joints and skin was determined. Anti‐P‐selectin mAb significantly reduced accumulation of monocytes (by 50%) and neutrophils (by 40%) in the talar joint, and of neutrophils in tail joints (by 90%). Anti‐E‐selectin mAb alone did not attenuate leukocyte migration, but when combined with anti‐P‐selectin mAb, it enhanced inhibition of neutrophil accumulation in the talar and carpal joints. In the same animals, anti‐P‐selectin mAb significantly inhibited neutrophil and monocyte migration to dermal inflammatory reactions induced by zymosan‐activated rat serum (ZAS) containing the chemotactic factor C5a des Arg , endotoxin (LPS), interferon‐γ (IFN‐γ) and tumor necrosis factor‐α (TNF‐α). In contrast, anti‐E‐selectin mAb alone had no effect on monocyte or neutrophil accumulation in inflamed skin of arthritic animals, but again enhanced the inhibition when combined with mAb to P‐selectin. The addition of anti‐L‐selectin mAb to anti‐P‐ and E‐selectin mAb did not further suppress monocyte or neutrophil migration to inflamed skin or joints. These results demonstrate that optimal leukocyte migration to arthritic joints and inflamed skin is P‐selectin dependent, and E‐selectin is not essential. However, E‐selectin contributes to migration when P‐selectin mechanisms are not operative. L‐selectin does not play a role in E‐ and P‐selectin‐independent leukocyte migration to joints or skin inflammation in arthritic rats. However, it is likely that additional selectin‐independent pathways also mediate neutrophil and monocyte migration to joint and skin inflammation.