Surfactant protein D decreases pollen-induced IgE-dependent mast cell degranulation

Abstract

(49). Surfactant has the following two known functions: a mechanical role in preventing alveolar collapse during breathing and a host defense role in lung innate immunity. Two of the four surfactant proteins have been shown to participate in host defense. SP-A and SP-D bind to bacteria, viruses, and fungi (12, 49) and enhance pathogen uptake by alveolar macrophages (38, 45), neutrophils (21), and dendritic cells (8). In addition, SP-A and SP-D are chemoattractants for alveolar macrophages (50) and neutrophils (13). Cytokine production by alveolar macrophages (36, 39) and dendritic cell maturation (7) are modulated by SP-A, and both SP-A and SP-D inhibit mitogen-stimulated lymphocyte proliferation (4 -6). These in vitro findings are corroborated by studies showing that SP-A and SP-D null mice are more susceptible to bacterial and viral infections than are wild-type animals (24 -27).SP-A and SP-D are members of the collectin family of proteins (12, 49). The collectins are composed of four domains, a short amino-terminal domain, a triple helical collagen region, a trimeric coiled-coil domain (neck), and a carboxy-terminal C-type lectin carbohydrate recognition domain (CRD; see Refs. 12 and 49). Binding of the collectins to bacteria is mediated in large part via interaction of the CRD with oligosaccharides on the pathogen (11). Both SP-A and SP-D are oligomeric and consist of three monomers that assemble into a trimer that undergoes further multimerization. Six SP-A trimers assemble in an octadecameric structure resembling a bouquet of tulips, whereas four trimers of SP-D form a dodecamer in the shape of a cruciform (12,49). Several functions of SP-A and SP-D have been shown to be dependent on their state of oligmerization (10,20).Although the effects of SP-A and SP-D on many types of innate and adaptive immune cells have been investigated, relatively little is known about their regulation of mast cell function. Mast cells, which reside at the interface of the host and the environment (skin, small intestine, lung), execute diverse functions that contribute to the immune response (1, 31). For example, mast cells have Fc⑀RI receptors that, when bound by IgE and cross-linked to an allergen, induce a signaling cascade leading to the release of mast cell granule contents (3,23). This degranulation process releases mediators, including histamine, which is a vasoactive amine that provokes a variety of responses that occur in allergy and asthma, such as vasodilatation and smooth muscle constriction (3). Until recently, mast cells were considered to be harmful to the host because of their key role in allergy and asthma. However, recent data have revealed that mast cells also contribute to host defense (32-34).A few recent studies have investigated interactions of surfactant proteins with allergens and regulation of allergenmediated cellular responses. For example, both SP-A and SP-D bind via their CRDs to dust mite allergens in a calciumdependent manner (47). This interaction of surfactant with dust mite allergens inhibits ...

Matrix Metalloproteinases in Lung: Multiple, Multifarious, and Multifaceted

“…Lung surfactant, which is primarily composed of 90% lipids and 10% proteins, coats the distal airspaces to reduce the alveolar surface tension, a process that is essential in prevention of atelectasis, and in host defense against environmental pathogens (92). Of the four surfactant-associated proteins that have been cloned in mammals, two with hydrophilic properties, surfactant protein (SP)-A and SP-D, play critical roles in innate host defense and adaptive immunity (156,306). rophages and stimulating the production of more MMPs, which could result in formation of bioactive proteins (Fig.…”

Segmental Allergen Challenge Alters Multimeric Structure and Function of Surfactant Protein D in Humans

“…Multimeric SP-D is capable of aggregation of allergens (7), lysis of microbes, enhancement of phagocytosis (8)(9)(10)(11), and modulation of cytokines and reactive oxygen species (12,13). SP-D is a regulator of pulmonary inflammation because it can activate macrophages and protect them from oxidative stress (14), and it is also able to inhibit allergen-induced activation of mast cells and basophils (15).…”

Surfactant protein D alters allergic lung responses in mice and human subjects

“…5 Furthermore, SP-A and SP-D inhibit in vitro lymphocyte proliferation, binding of allergen-specific IgE, and mast cell degranulation. [9][10] Treatment of mice with either recombinant or purified human SP-A or SP-D significantly decreases allergen-induced airway inflammation. 9,[11][12][13] Indeed, in a murine model of allergic bronchopulmonary aspergillosis, Madan et al 11 reported that treatment with pharmacologic doses of recombinant SP-D reduced cellular lung infiltration.…”