Modulation of acute inflammation by a chitin-binding lectin from Araucaria angustifolia seeds via mast cells.
The effects of a lectin (AaL) from seeds of Araucaria angustifolia were investigated in the model of rat paw edema. In vivo anti-and pro-inflammatory activities, role of sugar residues, inflammatory mediators and systemic toxicity were assessed. Intravenous injection of AaL (0.1-1 mg/kg) dose-dependently inhibited the dextran-induced increase in edema and vascular permeability, which were prevented by association of the lectin with its binding sugar N-acetyl-glucosamine (Glyc-Nac). AaL also significantly inhibited edema induced by serotonin (18%) and compound 48/80 (33%), but not edema induced by histamine. In contrast, when applied by the s.c. route, AaL evoked a paw edema that peaked 1 h later and was partially prevented by association with Glyc-Nac (59%) or by prior i.v. administration of the lectin itself (38.8%). This AaL edematogenic activity was significantly inhibited by pentoxifylline (44.4%) or dexamethasone (51%) and also by depletion of rat paw mast cells (45.6%), but not by L-N-nitro-arginine methyl ester or indomethacin, excluding involvement of nitric oxide and prostaglandins. Treatment of animals with a single anti-inflammatory dose of AaL (1 mg/kg, i.v.) for 7 days did not affect rat corporal mass, liver, kidney, spleen or stomach wet weight, blood leukocyte count, and urea, creatinine or serum transaminase activity. Systemic toxicity was apparent only at much higher doses (LD50=88.3 mg/kg) than those required for the anti-inflammatory effect. Summarizing, AaL exerts anti-and pro-edematogenic actions via interaction with its specific lectin domain. These actions may share a common pathway involving either activation or inhibition of inflammatory mediators from resident mast cells.
Mota
Mário R L
MR
Laboratório de Farmacologia dos Canais Iônicos -LAFACI-Instituto Superior de Ciências Biomédicas, Universidade Estadual do Ceará, Av. Paranjana 1700, 60740-000, Fortaleza-Ceará, Brazil.
Criddle
David N
DN
Alencar
Nylane M N
NM
Gomes
Raphaela C
RC
Meireles
Ana V P
AV
Santi-Gadelha
Tatiane
T
Gadelha
Carlos A A
CA
Oliveira
Cecília C
CC
Benevides
Raquel G
RG
Cavada
Benildo S
BS
Assreuy
Ana M S
AM
D000208:Acute Disease; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D002686:Chitin / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000517:prevention & control; D006632:Histamine / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000502:physiology*; D010431:Pentoxifylline / Q000494:pharmacology; D037121:Plant Lectins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012639:Seeds / Q000737:chemistry*; D012701:Serotonin / Q000494:pharmacology; D064028:Tracheophyta / Q000737:chemistry*; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D037121:Plant Lectins; D002686:Chitin; D012701:Serotonin; D003189:p-Methoxy-N-methylphenethylamine; D006632:Histamine; D010431:Pentoxifylline