Role of the Mac-1 and VLA-4 integrins, and concomitant Th2-cytokine production, in nitric oxide modulated eosinophil migration from bone marrow to lungs in allergic mice.
Although numerous studies demonstrate the participation of nitric oxide (NO) in various inflammatory diseases, the precise function of NO in allergic asthma remains unclear. We investigated whether iNOS inhibition could interfere with the kinetics of VLA-4 and Mac-1 expression and adhesion properties of bone marrow and peripheral blood eosinophils of sensitized mice after antigen exposure. Treatment of allergic mice with 1400 W (iNOS inhibitor) increased the adhesion of bone marrow eosinophils to ICAM-1, but not blood eosinophils, at 24h and 48 h after OVA-challenge. Conversely, adhesion of blood eosinophils from 1400 W-treated mice to VCAM-1 diminished at 24h and was almost completely blocked at 48 h. 1400 W did not induce any change in the adhesion of bone marrow eosinophils to VCAM-1, at 24h, but cells collected 48 h after challenge showed significantly lower adherence. Flow cytometry demonstrated that 1400 W resulted in a significantly increased Mac-1 expression on bone marrow eosinophils at 24h, as compared to control mice. However, at 24h, 1400 W significantly decreased Mac-1 and VLA-4 expressions on blood eosinophils. At 48 h, the expressions of both Mac-1 and VLA-4 returned to previous levels. Results show a temporal effect of iNOS upon Mac-1 expression and function, the chief adhesion molecule involved in the eosinophil efflux from the bone marrow at 24h. In contrast, Mac-1 and VLA-4 were involved in eosinophil mobilization from blood to lungs at 48 h after antigen challenge. Data suggest an important role of the Mac-1 and VLA-4 in the iNOS-modulated migration of eosinophils to the lungs of allergic mice.
Laboratory of Inflammation Research, São Francisco University, Bragança Paulista, SP, Brazil.
Edmar Henrique
EH
Pelaquini
Lucila de Assis Figueiredo
Lde A
Guimarães
Letícia Regina
LR
Benetti
Luiz Gustavo Romani
LG
Fernandes
Wirla Maria da Silva Cunha
WM
Tamashiro
Nicola
N
Conran
Heloisa Helena de Araujo
HH
Ferreira
D000578:Amidines / Q000494:pharmacology; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D001853:Bone Marrow / Q000187:drug effects / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D005260:Female; D006967:Hypersensitivity / Q000196:embryology / Q000276:immunology*; D039041:Integrin alpha4beta1 / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D007958:Leukocyte Count; D008168:Lung / Q000276:immunology*; D016177:Macrophage-1 Antigen / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000276:immunology / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D010047:Ovalbumin / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
D000578:Amidines; D001596:Benzylamines; D016207:Cytokines; D004791:Enzyme Inhibitors; D039041:Integrin alpha4beta1; D016177:Macrophage-1 Antigen; C104820:N-(3-(aminomethyl)benzyl)acetamidine; D009569:Nitric Oxide; D010047:Ovalbumin; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse