Eosinophil-associated lung diseases. A cry for surfactant proteins A and D help?

Abstract

Surfactant proteins (SP)-A and SP-D (SP-A/-D) play important roles in numerous eosinophil-dominated diseases, including asthma, allergic bronchopulmonary aspergillosis, and allergic rhinitis. In these settings, SP-A/-D have been shown to modulate eosinophil chemotaxis, inhibit eosinophil mediator release, and mediate macrophage clearance of apoptotic eosinophils. Dysregulation of SP-A/-D function in eosinophil-dominated diseases is also not uncommon. Alterations in serum SP-A/-D levels are associated with disease severity in allergic rhinitis and chronic obstructive pulmonary disease. Furthermore, oligimerization of SP-A/-D, necessary for their proper function, can be perturbed by reactive nitrogen species, which are increased in eosinophilic disease. In this review, we highlight the associations of eosinophilic lung diseases with SP-A and SP-D levels and functions.

Keywords: collectin; eosinophil; surfactant; surfactant protein-A; surfactant protein-D.

Figure 1.

Proposed model of eosinophil associated lung disease and surfactant protein A and D regulation. (A) In the airway, irritants are bound and cleared by surfactant protein (SP)-A, and cigarette smoke can alter the multimeric structure of SP-D. (B) Cytokines (IL-3, IL-5, and granulocyte macrophage-colony stimulating factor [GM-CSF]) released by T cells recruit eosinophils to the lung. Unbound eosinophils release proteolytic enzymes (eosinophil cationic protein [ECP], eosinophil peroxidase [EPO], major basic protein [MBP], and eosinophil associated RNase [EAR]) that cleave the multimeric structure of SP, resulting in free trimmers, and modify SP-A/-D activity. (C) In the distal airway, the inflammatory lung milieu (increased NO production) and the degradative enzymes released from the eosinophils (i.e., ECP, EPO) impair epithelial barrier permeability and SP-A/-D leak from the lumen into the tissue. (D) In an attempt to modulate eosinophilia, AT II cells increase synthesis and secretion of SP-A/-D. (E) Carbohydrate recognition domains of SP-A/-D multimeric structures (SP-A, octadecamer; SP-D, dodecamer) bind to eosinophils and prevent degranulation and cytokine production.