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Platelet‐activating factor: the effector of protein‐rich plasma extravasation and nitric oxide synthase induction in rat immune complex peritonitis
Author(s) -
Steil Ana Angelica,
Rodriguez Maria del Carmen Garcia,
Alonso Andrés,
Crespo Mariano Sanchez,
Bosca Lisardo
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb13288.x
Subject(s) - extravasation , nitric oxide , platelet activating factor , nitric oxide synthase , peritoneal cavity , chemistry , leukocyte extravasation , immune system , arginine , microbiology and biotechnology , immunology , biochemistry , inflammation , endocrinology , biology , amino acid , anatomy
1 The involvement of platelet‐activating factor (PAF) in immune complex‐induced/polymorphonuclear‐mediated tissue injury was studied by use of a reverse passive Arthus (RPA) model in the peritoneal cavity of rats. 2 Extravasation of protein‐rich plasma, accumulation of polymorphonuclear leukocytes (PMN), and the production of nitric oxide (NO) by resident peritoneal mononuclear phagocytes were assayed. 3 Treatment of rats with either UR‐12460 or BB‐823, two compounds which possess different chemical structures, but elicit the same antagonistic effect on the PAF receptor, abrogated protein‐rich plasma extravasation. In contrast, they did not show any effect on the accumulation of PMN. 4 Inhibition of NO production with both N G ‐mono methyl‐ l ‐arginine and N G ‐nitro‐ l ‐arginine failed to prevent protein‐rich plasma extravasation. 5 The production of NO by peritoneal adherent cells following RPA was measured in cells maintained for 2 to 28 h in culture, and it was significantly increased in cells removed as early as 15 min after RPA induction, as compared to controls. 6 Addition of 10 n m PAF to the culture medium reduced the generation of NO by peritoneal cells from RPA rats, whereas this mediator enhanced NO production in cells from naive control animals. 7 Treatment with either UR‐12460 or BB‐823 prior to the induction of RPA produced an almost complete inhibition of NO production. 8 Assay of nitric oxide synthase activity in cell homogenates from peritoneal cells showed that the activity was due to the inducible form of the enzyme. 9 Study by Northen blotting of mRNA coding for the inducible NO synthase (iNOS) showed transcription at 6 and 18 h after the induction of RPA, which was inhibited in UR‐12460‐treated rats. 10 These data indicate that PAF is the main mediator of the early plasma leakage observed in RPA, and also that PAF is implicated in the triggering of long‐term changes via induction of specific genes, as judged from its ability to promote the expression of iNOS.