Modulation of eosinophil migration from bone marrow to lungs of allergic rats by nitric oxide.
Chronic blockade of nitric oxide (NO) synthesis attenuates the eosinophil infiltration into airways of allergic rats. This study was designed to investigate whether the inhibition of eosinophil influx to the lung of allergic rats reflects modifications in the pattern of cell mobilization from the bone marrow to peripheral blood and/or to lung. Male Wistar rats were treated with N(omega)-nitro-l-arginine methyl ester (l-NAME; 20mg/rat per day) for 4 weeks and sensitized with ovalbumin (OVA). In control rats, the pulmonary OVA-challenge promoted an early (24h) increase in the bone marrow eosinophil population that normalized at 48 h after OVA-challenge, at which time the eosinophils disappeared from the blood and reached the lungs in mass. In l-NAME-treated rats, an accumulation of eosinophils in bone marrow was observed at 24 and 48 h post-OVA-challenge. No variation in this cell type number was observed in peripheral blood and bronchoalveolar lavage throughout the time-course studied. In control rats, the adhesion of bone marrow eosinophils to fibronectin-covered wells was significantly increased at 24h after OVA-challenge, whereas in l-NAME-treated rats the increased adhesion was detected at 48 h. A 32% decrease in the expression of inducible nitric oxide synthase (iNOS) (but not endothelial nitric oxide synthase; eNOS) in eosinophils from l-NAME-treated rats was observed. The levels of IgE, IgG(1) and IgG(2a) were not affected by the l-NAME treatment. Our findings suggest that inhibition of NO synthesis upregulates the binding of eosinophils to extracellular matrix proteins such as fibronectin, producing a delayed efflux of eosinophils from bone marrow to peripheral blood and lungs.
Ferreira
Heloisa Helena de Araujo
HH
Laboratory of Inflammation Research, São Francisco University, Bragança Paulista, São Paulo, Brazil. heloisaferreira@saofrancisco.edu.br
Costa
Rosana Aparecida de Oliveira
RA
Jacheta
Jerusa Maria
JM
Martins
Antonio Roberto
AR
Medeiros
Marta Valéria
MV
Macedo-Soares
Maria Fernanda
MF
De Luca
Iara Maria Silva
IM
Antunes
Edson
E
De Nucci
Gilberto
G
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects* / Q000502:physiology; D018893:Bronchoalveolar Lavage; D002465:Cell Movement / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004804:Eosinophils / Q000187:drug effects* / Q000502:physiology; D005353:Fibronectins / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006967:Hypersensitivity / Q000378:metabolism / Q000473:pathology*; D007136:Immunoglobulins / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000187:drug effects; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D020030:Nitric Oxide Donors; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D005353:Fibronectins; D007136:Immunoglobulins; D020030:Nitric Oxide Donors; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester