Surfactant Protein D: a new defence against pulmonary inflammation?

Surfactant protein D (SP-D) is a peptide synthesized by alveolar type II cells and by Clara cells of the distal airway. It is a member of collectins, a family of soluble proteins playing a role in the innate or non-antibody-mediated immune response. Taking into consideration that several in vitro studies demonstrate the protein's immunomodulatory properties and in vivo data show that alterations in SP-D expression can be induced by infectious and inflammatory stimuli, the distribution of SP-D in the distal respiratory tract becomes an ideal candidate for local regulation of lung inflammation. Studies on murine models showed that SP-D-deficient mice (SP-D -/-) present an increase in the baseline level of pulmonary inflammation and in many markers of immunoactivity, and also have alterations in surfactant phospholipid profiles. Moreover, variations in frequency of SP-D alleles are associated with differing host responses in humans to some pulmonary diseases such as chronic obstructive pulmonary disease.
On these pathophysiological basis, a group of the University of Philadelphia conducted a study to verify the effect of administration of intratracheal bleomycin (ITB), which is known to produce inflammatory response, on transgenic mice expressing varying levels of SP-D, in order to demonstrate the importance of SP-D in modulating inflammation during noninfectious lung injury.
In particular, eight-weeks old SP-D -/- mice and wild-type (WT) controls or SP-D-overexpressing (SP-D OE) mice and controls received either ITB, at increasing doses, or saline and were followed up to 21 days.
Statistical analysis demonstrated a dose-dependent decrease in survival in ITB SP-D -/- mice receiving 2 U/kg bleomycin, with a 14-d mortality of 100% versus 0% mortality for WT or SP-D -/- mice given saline. At 8 days, ITB SP-D -/- mice had greater respiratory distress (frequency/tidal volume) and weight loss than ITB WT mice. Furthermore, bronchoalveolar lavage cellularity, pulmonary parenchymal inflammation, and tissue 3-nitrotyrosine (NO₂Y) were increased to a greater extent in ITB SP-D -/- mice. By 21 days, compared with all groups, ITB SP-D -/- survivors had increased Trichrome staining and tissue hydroxyproline levels. On the contrary, and as a proof of principle, SP-D OE mice were highly resistant to bleomycin-induced morbidity and mortality at doses up to 3 U/kg.
Taken together, these findings highlight the emerging importance of the lung collectin SP-D in modulation of the inflammatory response after subacute lung injury. In fact, the injury in response to ITB is associated with an enhanced oxidative-nitrative stress in the lung, which produces parenchymal injury that can be modulated by the level of alveolar SP-D. According to these data and to other studies, inflammation in vivo appears to inversely correlate with alveolar levels of SP-D. Therefore, the administration of SP-D, either prophylactically or as therapy, may have the potential to limit the inflammatory response or might even have broader therapeutic implications in other forms for acute lung injury such as those produced by ischemia-reperfusion injury or hyperoxia.

Top