Resident Alveolar Macrophages Suppress, whereas Recruited Monocytes Promote, Allergic Lung Inflammation in Murine Models of Asthma

Abstract

The role and origin of alveolar macrophages (AMs) in asthma are incompletely defined. We sought to clarify these issues in the context of acute allergic lung inflammation utilizing house dust mite and ovalbumin murine models. Use of liposomal clodronate to deplete resident AMs (rAMs) resulted in increased levels of inflammatory cytokines and eosinophil numbers in lavage fluid and augmented histopathologic evidence of lung inflammation, suggesting a suppressive role of rAMs. Lung digests of asthmatic mice revealed an increased percentage of Ly6Chigh/CD11bpos inflammatory monocytes. Clodronate depletion of circulating monocytes, by contrast, resulted in an attenuation of allergic inflammation. A CD45.1/CD45.2 chimera model demonstrated that recruitment at least partially contributes to the AM pool in irradiated non-asthmatic mice, but its contribution was no greater in asthma. Ki-67 staining of AMs supported a role for local proliferation, which was increased in asthma. Our data demonstrate that rAMs dampen, while circulating monocytes promote, early events in allergic lung inflammation. Moreover, maintenance of the AM pool in the early stages of asthmatic inflammation depends on local proliferation but not recruitment.

Secreted PLA2 group X orchestrates innate and adaptive immune responses to inhaled allergen

“…A notable finding in our study was that the lack of Pla2g10 markedly altered the number of recruited macrophages to the lung -a significant finding, given recent studies that have demonstrated that recruited macrophages are central to the promotion of allergic inflammation (39,72), while resident macrophages, which were not altered by the loss of Pla2g10, tend to suppress allergic inflammation (73,74). Since our group and others have clearly demonstrated that human and murine macrophages express PLA2G10/Pla2g10 (1, 75, 76), fur-ther work will be needed to ascertain whether these functions are due to the loss of sPLA 2 -X within macrophages or to the lack of macrophage activation by sPLA 2 -X.…”

Neonatal Pulmonary Macrophage Depletion Coupled to Defective Mucus Clearance Increases Susceptibility to Pneumonia and Alters Pulmonary Immune Responses

“…In the allergic models, MF depletion attenuated, rather than enhanced, goblet cell metaplasia and other Th2 inflammatory responses in the absence of bacterial pneumonia (25,39,40).…”

Revisão Sistemática Sobre Modelos Experimentais De Asma Aguda E Crônica Induzidos Com Extrato De Ácaro Da Poeira Doméstica

“…Nos artigos selecionados observou-se que o modelo agudo foi usado em dez artigos. Os resultados mostram, em relação ao desfecho inflamatório no pulmão, que os grupos expostos ao HDM apresentam percentual elevado de eosinófilos, alto número de células nas contagens total, inflamação das vias aéreas, produção de células caliciformes, hiper-responsividade das vias aéreas, IgE total no soro, aumento de citocinas IL-4 e IL-5 e alto influxo celular na área peribronquial e perivascular 14,16,18,19,21,23,[24][25][26]29 . Em relação à função pulmonar, o trabalho de Phipps et al 26 mostra um aumento da resistência e diminuição da complacência das vias aéreas.…”

“…Portanto, depreende-se que o modelo agudo de exposição ao HDM é um método importante para avaliar e obter resultados preliminares e sem uso de adjuvante. Os desfechos inflamatórios no tecido pulmonar são baseados em eosinófilos 16,19,24,25 . Por outro lado, modelos crônicos de exposição ao alérgeno assemelham-se ao modelo agudo 10 .…”

“…Observa-se na Tabela 1 que a dose mais usada foi de 100µg. Os resultados desses trabalhos mostram que o número de células totais e diferenciais no lavado broncoalveolar (BAL) é significativamente alto, assim como a inflamação das vias aéreas e a produção de células caliciformes 16,19,23,29 . A contagem total e diferencial das células, o nível de IgE no soro e a resistência das vias aéreas à metacolina também são elevadas.…”