Mechanisms involved in the rat peritoneal leukocyte migration induced by a Kunitz-type inhibitor isolated from Dimorphandra mollis seeds.
DMTI-II is a Kunitz-type inhibitor isolated from Dimorphandra mollis seeds that causes rat inflammatory edema by mechanisms involving activation of mast cells and sensory C-fibers. The present study aimed to further explore the inflammatory mechanisms involved in DMTI-II-induced inflammation, focusing to the leukocyte migration in vivo. Male Wistar rats (250-280 g) were injected with DMTI-II (1-100microg/cavity), and at 4-24h thereafter the leukocyte counts in peritoneal lavage were evaluated. DMTI-II caused dose- and time-dependent accumulation of neutrophils and eosinophils. The peritoneal neutrophil influx initiated at 4h, achieving maximal responses at 16 h after DMTI-II injection (16- and 22-fold increase, respectively). The DMTI-II-induced eosinophil recruitment was observed as early as 4h achieving the maximal responses at 16 h (12- and 17-fold increase, respectively). The mononuclear cell number increased at 4h and 16 h (1.5-fold and 1.6-increase, respectively). Prior treatments with dexamethasone, the cyclooxygenase (COX) inhibitors indomethacin and celecoxib, as well as the PAF receptor antagonist PCA4248 largely reduced the neutrophil and eosinophil accumulation. The selective lypoxygenase inhibitor AA861, the tachykinin NK(1) antagonist SR-140333 and the nitric oxide inhibitor L-NAME reduced only the eosinophil number. The eotaxin levels were significantly higher in DMTI-II-injected rats compared with control animals. In conclusion, DMTI-II causes an early migration of eosinophils and neutrophils by mechanisms involving COX-2- and lipoxygenase-derived metabolites, PAF, substance P and NO. The capacity of DMTI-II to recruit eosinophils at early times is likely to reflect the allergen properties of proteinase inhibitors belonging to Kunitz family.
Mello
Gláucia C
GC
Department of Pharmacology of Faculty of Medical Sciences, State University of Campinas (UNICAMP), P.O. Box 6111, 13084-971 Campinas (SP), Brazil. glaumello@yahoo.com.br
Desouza
Ivani A
IA
Mariano
Nádia S
NS
Ferreira
Tatiane
T
Macedo
Maria Lígia R
ML
Antunes
Edson
E
D000704:Analysis of Variance; D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology; D000068579:Celecoxib; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D003907:Dexamethasone / Q000494:pharmacology; D007887:Fabaceae / Q000737:chemistry*; D007213:Indomethacin / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced*; D007962:Leukocytes / Q000166:cytology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010455:Peptides / Q000378:metabolism* / Q000633:toxicity*; D010533:Peritoneal Lavage; D010880:Piperidines / Q000494:pharmacology; D010940:Plant Proteins / Q000378:metabolism* / Q000633:toxicity*; D011720:Pyrazoles / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012639:Seeds / Q000737:chemistry*; D013449:Sulfonamides / Q000494:pharmacology
D016227:Benzoquinones; C053865:Kunitz-type protease inhibitor, plant; D010455:Peptides; D010880:Piperidines; D010940:Plant Proteins; D011720:Pyrazoles; D011812:Quinuclidines; D013449:Sulfonamides; C085215:SR 140333; D003907:Dexamethasone; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; D000068579:Celecoxib; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin