Interleukin-1-induced leukocyte extravasation across rat mesenteric microvessels is mediated by platelet-activating factor.

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: United States NLM ID: 7603509 Publication Model: Print Cited Medium: Print ISSN: 0006-4971 (Print) Linking ISSN: 00064971 NLM ISO Abbreviation: Blood Subsets: MEDLINE
    • Publication Information:
      Publication: 2021- : [New York] : Elsevier
      Original Publication: New York, Grune & Stratton [etc.]
    • Subject Terms:
      Receptors, Cell Surface* ; Receptors, G-Protein-Coupled*; Chemotaxis, Leukocyte/*drug effects ; Interleukin-1/*pharmacology ; Mesentery/*blood supply ; Platelet Activating Factor/*physiology; Animals ; Azepines/pharmacology ; Cell Adhesion/drug effects ; Dihydropyridines/pharmacology ; Edema/chemically induced ; Imidazoles/pharmacology ; Inflammation ; Interleukin-1/toxicity ; Leukocytes/drug effects ; Leukocytes/physiology ; Male ; Microcirculation ; N-Formylmethionine Leucyl-Phenylalanine/pharmacology ; N-Formylmethionine Leucyl-Phenylalanine/toxicity ; Platelet Membrane Glycoproteins/antagonists & inhibitors ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins/pharmacology ; Skin/drug effects ; Skin/pathology ; Triazoles/pharmacology
    • Abstract:
      Although our understanding of the molecular interactions that mediate the adhesion of leukocytes to venular endothelial cells has greatly expanded, very little is known about the mechanisms that mediate the passage of leukocytes across the vessel wall in vivo. The aim of the present study was to investigate the role of endogenously formed platelet-activating factor (PAF) in the process of leukocyte extravasation induced by interleukin-1 (IL-1). To determine at which stage of emigration PAF was involved, we studied the behavior of leukocytes within rat mesenteric microvessels by intravital microscopy. Rats were injected intraperitoneally with saline, recombinant rat IL-1 beta (IL-1 beta), or the peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) 4 hours before the exteriorization of the mesenteric tissue. In animals treated with IL-1 beta there was a significant increase in the number of rolling and adherent leukocytes within venules (20- to 40-micron diameter) and in the number of extravasated leukocytes in the tissue. Pretreatment of rats with the PAF receptor antagonist UK-74,505 had no effect on the leukocyte responses of rolling and adhesion, but significantly inhibited the migration of the leukocytes across the vessel wall induced by IL-1 beta (76% inhibition). A structurally unrelated PAF antagonist, WEB-2170, produced the same effect (64% inhibition). However, in contrast, UK-74,505 had no effect on the leukocyte extravasation induced by FMLP, indicating selectivity for the response elicited by certain mediators. These results provide the first line of direct evidence for the involvement of endogenously formed PAF in the process of leukocyte extravasation induced by IL-1 in vivo.
    • Grant Information:
      United Kingdom Wellcome Trust
    • Accession Number:
      0 (Azepines)
      0 (Dihydropyridines)
      0 (Imidazoles)
      0 (Interleukin-1)
      0 (Platelet Activating Factor)
      0 (Platelet Membrane Glycoproteins)
      0 (Receptors, Cell Surface)
      0 (Receptors, G-Protein-Coupled)
      0 (Recombinant Proteins)
      0 (Triazoles)
      0 (platelet activating factor receptor)
      1DMI0E5023 (modipafant)
      59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
      CKS724B66O (bepafant)
    • Publication Date:
      Date Created: 19950501 Date Completed: 19950531 Latest Revision: 20210216
    • Publication Date:
      20231215
    • Accession Number:
      7727783