Quantitative and qualitative differences in bronchoalveolar inflammatory cells inPseudomonas aeruginosa-resistant and -susceptible mice

Abstract

SUMMARYThe difference in severity of Pseudomonas aeruginosa-induced chronic lung infection may be determined by differences in host in¯ammatory responses. In the present study we investigate this possibility using BALB/c and C57Bl/6 mice, resistant and susceptible, respectively, to chronic lung infection with P. aeruginosa. Following intratracheal inoculation of P. aeruginosa-impregnated agar beads, C57Bl/6 mice mounted a stronger in¯ammatory response with signi®cantly higher total cell numbers in the bronchoalveolar lavage¯uid compared with BALB/c mice. While polymorphonuclear leucocytes were the predominant cell in C57Bl/6 mice, macrophages constituted the majority in BALB/ c mice at day 7 post-infection. Alveolar macrophages from C57Bl/6 mice showed signi®cantly higher spontaneous production of nitric oxide (NO) at day 7 post-infection compared with BALB/c mice. Following in vitro stimulation with heat-killed Pseudomonas antigen, these cells produced signi®cantly higher NO compared with cells from BALB/c mice at day 21 post-infection. Production of tumour necrosis factor-alpha (TNF-a) by alveolar macrophages was signi®cantly higher at day 7 in BALB/c mice compared with C57Bl/6 mice, which showed signi®cantly higher levels at day 28 post-infection. Taken together, these results suggest that defects in the host in¯ammatory process contribute to the variable outcome of chronic lung infection with P. aeruginosa. An exaggerated in¯ammatory response dominated by polymorphonuclear cells correlates with susceptibility to infection, whilst a modest in¯ammatory response dominated by macrophages correlates with resistance. Moreover, the quantity and timing of production of NO and TNF-a by alveolar macrophages may modulate the course and outcome of infection.

Defective Phagocytosis and Clearance of Pseudomonas aeruginosa in the Lung Following Bone Marrow Transplantation

“…5). TNF-␣ is a critical cytokine for the elimination of P. aeruginosa (19,20). Previous data have demonstrated that the immunosuppression associated with cecal ligation and puncture (CLP) models of sepsis is associated with defective production of TNF-␣ by AMs.…”

“…The transient transgenic expression of TNF-␣ within the lungs of CLP animals improves AM phagocytic function and protects from P. aeruginosa infection (19,20). Further experimental evidence for the importance of AMs and TNF-␣ production in the clearance of P. aeruginosa come from studies examining chronic P. aeruginosa infection in resistant (BALB/c) vs susceptible (C57BL/6) strains of mice (19,20). These experiments demonstrated that TNF-␣ production by AMs was significantly higher in resistant BALB/c mice on day 7 postinfection than in susceptible C57BL/6 mice.…”

“…TNF-␣ is a critical cytokine necessary for effective clearance of P. aeruginosa by AMs (19,20). We compared the ability of AMs from BMT and wild-type mice to produce TNF-␣ both basally and in response to endotoxin stimulation.…”

IL-10 delivery by AAV5 vector attenuates inflammation in mice with pseudomonas pneumonia

“…In non-CF mice, infection with P. aeruginosa-laden beads can persist for up to 28 days, 22,46,47 whereas CFTR knockout mice appear to have more severe mortality and inflammation, characterized by high levels of proinflammatory mediators (TNF-a, KC and MIP-2) 3 days after exposure to the beads. Between days 3 and 7 after infection with P. aeruginosa-laden beads in CF mice, the process of bacterial killing is Figure 4 Inflammation-associated pathology is reduced in AAV5.Cb-mIL10-treated mice.…”

Lipopolysaccharide-Induced Osteoclastogenesis from Mononuclear Precursors: A Mechanism for Osteolysis in Chronic Otitis

“…However, Oc formation in this study occurred only in Balb/c and not C57BL/ 6 mice, the animals used in our study. Previous studies have demonstrated that Balb/c and C57BL/6 mice mount different responses to inflammatory stimuli (Sapru et al 1999). Such differences likely contributed to these conflicting results.…”