Inhibition of CL-11 reduces pulmonary inflammation in a mouse model of Klebsiella pneumoniae lung infection.

Infection caused by K. pneumoniae is associated with severe inflammation due to stimulation of the innate immune components including the complement system, which is the main player of the innate immune response. Excessive complement-mediated inflammation may cause severe lung injury. Here we clearly show that K. pneumoniae binds to different lectin pathway carbohydrate recognition molecules and activates the complement cascade via the LP. Administration of anti-CL-11 antibodies 6 h before the infection impairs LP functional activity but it shows no effect on the survival time of mice infected with K. pneumoniae. Similarly, no significant difference in bacterial load in blood and lung tissues was observed between mice that received anti-CL-11 and control group treated with an isotype antibody. Interestingly, treatment of mice with anti-CL-11 prior to infection significantly improved histopathological changes and lung injury score induced by K. pneumoniae. Moreover, administration of anti-CL-11 reduced leukocytes infiltration into lung tissues and decreased the levels of the inflammatory mediators TNF-α, IL-6, and IL-1ß in the infected mice. These findings indicate that inhibition of the LP could secure a significant level of protection against lung injury during the infection caused by K. pneumoniae.

Recombinant chemotaxis inhibitory protein of Staphylococcus aureus (CHIPS) protects against LPS-induced lung injury in mice.

Acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS) are clinical conditions caused by trauma, lung infection or sepsis. ALI/ARDS is associated with massive recruitment of neutrophils into the lung with release of reactive oxygen species and excessive inflammatory response that damage alveolar tissue. Here we report the successful use of a potent recombinant chemotaxis inhibitory protein (rCHIPS) derived from Staphylococcus aureus in reducing the severity of ALI/ARDS. Treatment with rCHIPS reduces pulmonary inflammation and permeability in mice after intranasal administration of lipopolysaccharide (LPS). rCHIPS treatment significantly reduces lung myeloperoxidase (MPO) activity, pro-inflammatory cytokines, broncho-alveolar lavage (BAL) fluid protein content as well as histopathological changes. In addition, treatment with rCHIPS significantly diminishes neutrophils and leukocytes recruitment into lung tissue after LPS administration and hence protects mice from reactive oxygen species mediated lung injury. Our finding reveals potential therapeutic benefits of using rCHIPS for the treatment of ALI/ARDS.