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Involvement of leukotrienes, TNF‐α, and the LFA‐1/ICAM‐1 interaction in substance P‐induced granulocyte infiltration
Author(s) -
Saban Marcia R.,
Saban Ricardo,
Bjorling Dale,
HaakFrendscho Mary
Publication year - 1997
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.61.4.445
Subject(s) - tumor necrosis factor alpha , eosinophil , leukotriene b4 , degranulation , biology , granulocyte , icam 1 , in vivo , cytokine , eicosanoid , leukotriene , endocrinology , medicine , inflammation , immunology , cell adhesion molecule , biochemistry , receptor , enzyme , microbiology and biotechnology , asthma , arachidonic acid
Substance P (SP) has been shown to mediate granulocyte infiltration into the mouse skin by inducing mast cell degranulation. In this study, using a variety of specific inhibitors, we investigated the cascade of events involved in the response of neutrophils and eosinophils to SP. The prostaglandin inhibitor, indomethacin, had little effect on SP‐induced leukocyte migration. In contrast, pretreatment with the leukotriene (LT) synthesis inhibitor, A‐64077, completely blocked neutrophil but not eosinophil migration in response to SP. Participation of tumor necrosis factor α (TNF‐α) and LFA‐1/ICAM‐1 interaction was confirmed by inhibition of SP‐induced leukocyte migration by pretreatment of mice with monoclonal antibodies to TNF‐α, LFA‐1, and ICAM‐1. Moreover, alteration in leukocyte migration by indomethacin was found to depend on the concentration of TNF‐α used. Indomethacin did not alter the number of leukocytes induced by low concentrations of TNF‐α (0.1 ng), but reduced the number of cells stimulated with high TNF‐α concentrations (1.0 ng). These results support the concept that SP modulates in vivo neuroinflammatory responses, as measured by granulocyte migration, initiating a cascade of events that includes LT production, TNF‐α secretion, and engagement of LFA‐1 and ICAM‐1. J. Leukoc. Biol . 61: 445–451; 1997.