Alterations in lung collectins in an adaptive allergic immune response

Abstract

Adaptive immunity involves antigen-specific receptors and requires hours to days for differentiation of effector cells. In contrast, innate immunity involves pattern recognition receptors, and the effector stage occurs within minutes to hours of exposure. Although adaptive antigenic responses are known to play essential roles in allergic asthma, the role of innate immunity is less well characterized.Innate responses involve many cell types and mediators, including surfactant apoproteins (8,9,14,38,40,55). The best known function of surfactant and the surfactant apoproteins is to decrease the surface tension in the alveoli. However, surfactant apoproteins also modulate pulmonary inflammatory responses (8,14,40,55).Two of the surfactant apoproteins, surfactant A (SP-A) and surfactant D (SP-D), are collectins. The collectins are a family of proteins characterized by a collagen-like region and a C-type lectin at their carboxy terminus (20), which also includes mannose-binding protein (18)(19)(20)38). The collectins are important mediators of innate immunity, with their functions including opsonizing bacteria and promoting phagocytosis; mannose-binding protein has also been demonstrated to activate complement (8,20).SP-A and SP-D can modulate innate immune responses in the lung. Both SP-A and SP-D can bind and opsonize bacteria (28,32,48) and fungi (1,9,17,34,37,39,42,44,46,47,54). In addition, SP-A can bind viruses such as influenza A and herpes simplex (35, 49, 50) as well as Pneumocystis carinii (57) and is a chemoattractant for macrophages (56). Mice deficient in SP-A are more susceptible to infections resulting from Pseudomonas (30) and Streptococcus (31) compared with wild-type mice. Moreover, SP-A expression is induced during lung inflammation after exposures that include lipopolysaccharide (LPS), bleomycin, and silica (51).Although allergic pulmonary responses are clearly dependent on adaptive immune responses, the relationship of innate mediators to these responses has not been characterized extensively. Given the potential role of surfactant apoproteins in innate and adaptive in vivo responses, we asked whether the surfactant apoproteins are involved in the pulmonary response to allergen. To investigate pulmonary adaptive responses, we analyzed an in vivo murine model of asthma, elicited by systemic sensitization to the allergen ovalbumin (OVA) followed by aerosolized challenge, resulting in eosinophilic pulmonary infiltrates and airway hyperresponsiveness (AHR; see Refs. 11,26,27,36). We hypothesized that immune responses

Major House Dust Mite Allergens Dermatophagoides pteronyssinus 1 and Dermatophagoides farinae 1 Degrade and Inactivate Lung Surfactant Proteins A and D

“…There is no doubt that chronic exposure, which is so characteristic of HDM sensitivity, would result in the cumulative build up and continuous replenishment of very high concentrations of allergens in lung tissues. Despite some reported increases in SP-A and SP-D levels 24 h after allergen challenge, which may well represent an innate immune defense mechanism (11,12,15,59), given our findings, we believe that as well as very short-term exposure, which has been discussed above, long-term exposure to HDM allergens would disrupt the physiological levels and functions of SP-D in the lungs, and this could have profound consequences. Consistent with this, decreased levels of SP-A and SP-D in BALF are seen in the chronic phase of allergen exposure in murine models of allergic hypersensitivity to HDM allergens (58).…”

“…SP-A and SP-D levels increase severalfold in allergic asthma (11)(12)(13), and furthermore, the kinetics of the increase in SP-D levels after allergen challenge have been reported to coincide with the resolution of inflammation (14). Mouse models of house dust mite (Dermatophagoides pteronyssinus (Der p)) allergy have clearly demonstrated a protective role for SP-D during secondary allergen exposure.…”

The Costimulatory Molecule SLAM Is Critical for Pulmonary Allergic Responses

“…Mice were sensitized and challenged with allergen ovalbumin (OVA) as previously described (4,(10)(11)(12)(13)(14)(15). Briefly, mice were sensitized by intraperitoneal injection with 10 g chicken OVA and 1 mg Al(OH) 3 (alum) on Days 0 and 7.…”

“…Each mouse underwent BAL, as previously described (4,(10)(11)(12)(13)(14)(15). Cells were resuspended in RPMI.…”

“…Mice were placed in individual chambers, and 100 mg/ml methacholine was nebulized into the chambers via an inlet for 2 min as previously described (10,(15)(16)(17). Readings were averaged over 7 min from the beginning of the nebulization.…”