The alveolar macrophage (AM) is believed to be of central importance in the immune response against infection and tumour. analysis demonstrated that individuals with small cell carcinoma were the only group that showed a decrease in MHC class II surface manifestation. Surface manifestation of ICAM-1 and CD83 was decreased on AM from individuals with large, squamous and small cell carcinoma compared to settings but not adenocarcinoma. Mannose receptor levels were only decreased on AM from individuals with squamous and small cell carcinoma but not adenocarcinoma and large cell undifferentiated carcinoma. We conclude that there are type-specific alterations in uptake ability, cytokine secretion and phenotype of AM from lung malignancy individuals, which may result in an failure to stimulate anti-tumour immunity. The observed variations between lung malignancy subgroups may clarify previously reported inconsistencies in descriptions of AM characteristics in lung malignancy. < 0001 to indicate Nutlin-3 a highly significant difference, and < 005 to indicate a significant difference. Results Uptake of polystyrene particles by AM AM from control individuals were able to take up the majority of 40 nm beads after 24 h (81% 11%). AM from individuals with squamous cell carcinoma (39% 20%) and small cell carcinoma (29% 11%) were impaired in their ability to take up 40 nm beads compared Nutlin-3 to control individuals (Fig. 1a). AM from individuals with adenocarcinoma (63% 19%) and large cell undifferentiated carcinoma (62% 18%) showed related uptake of 40 nm beads to control individuals < 005 for adenocarcinoma, squamous and large cell carcinoma; < 001 for small cell carcinoma) compared to control individuals (Fig. 1b). Representative dot plots of 40 and 1000 nm fluorescent bead uptake from one patient in each study group is demonstrated (Fig. 1c). Fig. 1 Uptake of different size particles by AM. AM from BAL samples from adenocarcinoma (adeno) (= 4), small cell carcinoma (small) (= 5), squamous cell carcinoma (squamous) (= 4) and large cell undifferentiated carcinoma (large) (= 6) compared to control ... Cytokine production by AM We analysed the cytokine production of LPS triggered AM from lung malignancy individuals compared to noncancer individuals (Fig. 2). There was no detectable IL-10 in AM supernatants from individuals with small, large and squamous cell carcinoma (< 10 pg/ml) (Fig. 2a). IL-10 levels were low but measurable in control patients and there was no significant difference between control (60 54 pg/ml) and adenocarcinoma patients (53 40 pg/ml) (Fig. 2a). Secretion of IL-1 was CLG4B greatly decreased from AM of patients with small cell (22 19 pg/ml, < 005), large cell (6 6 pg/ml, < 005) and squamous cell carcinomas (19 5 pg/ml, < 005) but not adenocarcinoma (261 122 pg/ml) compared to control patients (504 265 Nutlin-3 pg/ml) (Fig. 2b). TNF- was decreased in AM from all Nutlin-3 groups of lung malignancy patients except adenocarcinoma (Fig. 2c), however, only AM from patients with small (74 98 pg/ml, < 005) and large cell carcinoma (89 755 pg/ml, < 005) showed a decrease in IL-6 secretion (Fig. 2d). Fig. 2 Cytokine secretion profiles of AM. AM from BAL samples from adenocarcinoma (adeno) (= 6), small cell carcinoma (small) (= 5), squamous cell carcinoma (squamous) (= 6) and large cell undifferentiated carcinoma (large) (= 7) compared to control ... Phenotype of AM Phenotypic analysis of AM from patients with adenocarcinoma, small, squamous and large Nutlin-3 cell undifferentiated carcinoma compared to control patients (= 12) was decided (Figs 3 and ?and4).4). Phenotypic expression.

The alveolar macrophage (AM) is believed to be of central importance
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