Effects of MK-801 and amphetamine treatments on allergic lung inflammatory response in mice

Autor(es)

Hamasato, Eduardo Kenji ^[1] ; Ligeiro de Oliveira, Ana Paula ^[2] ; Lino-dos-Santos-Franco, Adriana ^[3] ; Ribeiro, Alison ^[1] ; de Paula, Viviane Ferraz ^[1] ; Schatzmann Peron, Jean Pierre ^[4] ; Damazo, Amilcar Sabino ^[5] ; Tavares-de-Lima, Wothan ^[6] ; Palermo-Neto, Joao ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Pathol, Sch Vet Med, Neuroimmunomodulat Res Grp, BR-05508270 Sao Paulo - Brazil

^[2] Nove Julho Univ, Post Grad Program Biophoton Appl Hlth Sci, UNINOVE, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Dept Clin & Toxicol Anal, Fac Pharmaceut Sci, BR-05508270 Sao Paulo - Brazil

^[4] Univ Sao Paulo, Dept Immunol, BR-05508270 Sao Paulo - Brazil

^[5] Fed Univ Cuiaba, Fac Med Sci, Dept Basic Sci Hlth, Cuiaba - Brazil

^[6] Univ Sao Paulo, Dept Pharmacol, BR-05508270 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: International Immunopharmacology; v. 16, n. 4, p. 436-443, AUG 2013.
• Citações Web of Science: 9

Resumo

Glutamate acts as a neurotransmitter within the Central Nervous System (CNS) and modifies immune cell activity. In lymphocytes, NMDA glutamate receptors regulate intracellular calcium, the production of reactive oxygen species and cytokine synthesis. MK-801, a NMDA receptor open-channel blocker, inhibits calcium entry into mast cells, thereby preventing mast cell degranulation. Several lines of evidence have shown the involvement of NMDA glutamate receptors in amphetamine (AMPH)-induced effects. AMPH treatment has been reported to modify allergic lung inflammation. This study evaluated the effects of MK-801 (0.25 mg/kg) and AMPH (2.0 mg/kg), given alone or in combination, on allergic lung inflammation in mice and the possible involvement of NMDA receptors in this process. In OVA-sensitized and challenged mice, AMPH and MK-801 given alone decreased cellular migration into the lung, reduced IL-13 and IL10 levels in BAL supernatant, reduced ICAM-1 and L-selectin expression in granulocytes in the BAL and decreased mast cell degranulation. AMPH treatment also decreased IL-5 levels. When both drugs were administered, treatment with MK-801 reversed the decrease in the number of eosinophils and neutrophils induced by AMPH in the BAL of OVA-sensitized and challenged mice as well as the effects on the expression of L-selectin and ICAM-1 in granulocytes, the IL-10, IL-5 and IL-13 levels in BAL supernatants and increased mast cell degranulation. At the same time, treatment with MK-801, AMPH or with MK-801 + AMPH increased corticosterone serum levels in allergic mice. These results are discussed in light of possible indirect effects of AMPH and MK-801 via endocrine outflow from the CNS (i.e., HPA-axis activity) to the periphery and/or as a consequence of the direct action of these drugs on immune cell activity, with emphasis given to mast cell participation in the allergic lung response of mice. (c) 2013 Elsevier B.V. All rights reserved. (AU)

• Processo FAPESP: 09/01826-4 - Participação glutamatérgica e encefalinérgica nos efeitos induzidos pela anfetamina na resposta inflamatória alérgica pulmonar de camundongos
• Beneficiário: Eduardo Kenji Hamasato
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 09/51886-3 - Neuroimunomodulação: fármacos, estresse e citocinas nas relações entre os sistemas nervoso, endócrino e imune
• Beneficiário: João Palermo Neto
• Modalidade de apoio: Auxílio à Pesquisa - Temático